Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8489544 | Susceptibility to relapsing polychondritis is associated with HLA-DR4. | 1993 May | OBJECTIVE: To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP). METHODS: HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement-dependent microcytotoxicity assay. HLA-DR genotyping of 12 DR4-positive RP patients and 57 controls was performed by allele-specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction. RESULTS: A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (Pcorr < 0.001). Genotyping of DR4-positive patients and controls revealed no predominance of any DR4 subtype. CONCLUSION: There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions. | |
| 8432914 | HLA antigens in anti-Ro(SS-A)-positive patients with recurrent annular erythema. | 1993 Feb | BACKGROUND: Recurrent annular erythema associated with the anti-Ro(SS-A) antibody response has recently been reported in Orientals. The association is assumed to represent a distinct clinical entity. OBJECTIVE: Our purpose was to extend knowledge on the immunogenetic spectrum of the disease. METHODS: Sixteen anti-Ro(SS-A)-positive Japanese patients with recurrent annular erythema and Sjögren's syndrome were studied. The standard complement-dependent microcytotoxicity assay was used to type the HLA-A, -B, -C, -DR, and -DQ, as well as the HLA-DRw52 and -DRw53 antigens. RESULTS: All 16 patients were positive for HLA-DRw52 antigens as compared with 52% of control subjects (p < 0.01 relative risk 14.8). No significant deviations were noted in the phenotype frequencies for HLA-A, -B, -C, and -DQ antigens. CONCLUSION: HLA-DRw52 is closely related to annular erythema in anti-Ro(SS-A)-positive Japanese patients with Sjögren's syndrome. | |
| 1352097 | Primary Sjögren's syndrome with antibodies to HTLV-I: clinical and laboratory features. | 1992 Jun | The prevalence of antibodies to human T lymphotropic virus type I (HTLV-I) was studied in patients with primary Sjögren's syndrome. Thirteen of 36 serum samples were positive by enzyme linked immunosorbent assay (ELISA) and particle agglutination assay for antibodies to HTLV-I and were confirmed by western blotting. The presence of antibodies to HTLV-I may signify an HTLV-I carrier state. These patients had a high occurrence of extraglandular manifestations such as uveitis, myopathy, and recurrent high fever compared with patients who did not have antibodies to HTLV-I. Patients with antibodies to HTLV-I had an increased spontaneous proliferation of peripheral blood mononuclear cells compared with those without the antibodies. The proportions of activated and memory T cells (HLA-DR+ CD3+, CD25+ CD3+, and CD29+ CD4+ cells) were higher in HTLV-I carriers than in non-carriers. The presence of antibodies to HTLV-I in some patients with primary Sjögren's syndrome suggests that HTLV-I may cause primary Sjögren's syndrome or its extraglandular manifestations, or both. | |
| 1370417 | Specificity and T cell receptor beta chain usage of a human collagen type II-reactive T ce | 1992 Jan | Collagen type II (CII) is a cartilage-specific matrix compound well known as an inducer of an experimental, T cell-dependent autoimmune arthritis, a disease which shows some similarities to human rheumatoid arthritis. Here we report on an HLA-DR7-restricted human CD4 T cell clone (TC9), which was isolated from a healthy donor and recognizes human CII. After screening CNBr fragments of CII and tryptic fragments derived thereof, the T cell epitope could be mapped to amino acid residues 271-285 of the triple helical region of CII that are located within CNBr fragment 11 [alpha 1 (II) CB11]. This epitope was confirmed by a synthetic peptide stimulatory for TC9. The T cell receptor beta chain of TC9 was cloned using the polymerase chain reaction; it comprises V beta 6.7 and contains besides J beta 2.3 and C beta 2 an as yet undescribed sequence for the D segment. | |
| 8082485 | Phenotypic and functional abnormalities in the peripheral blood T-cells of patients with p | 1994 Mar 15 | Changes in regulatory T-cell subset (including the recently described CD4 helper inducers or suppressor inducers) balance in the peripheral blood may play a role in the pathogenesis of primary Sjogren's syndrome (SS). Direct immunofluorescence and flow cytometry were used to quantitate and analyse peripheral blood lymphocytes in 15 patients with primary SS and 15 control subjects. A reduction in the percentage of circulating CD4 lymphocytes was observed in patients with SS. There was no quantitative abnormality in the percentage of circulating CD4+ 2H4+ (suppressor inducer), CD4+ 4B4+ (helper inducer), CD2, CD3, CD8, CD8+ 2H4+, CD8+ 4B4+, CD25 (IL-2R), CD19, CD16, CD57 lymphocytes in the patients. Circulating CD8 lymphocytes expressing the activation marker HLA-DR were increased in the patients. The functional status of peripheral blood lymphocytes was assessed by PHA (phytohaemagglutinin) stimulation followed by monitoring their proliferative response by radiolabelled thymidine uptake and expression of CD25 (Interleukin-2 receptor). A reduction in the proliferative response of total, CD4-depleted, and CD8-depleted lymphocytes suspensions to PHA was demonstrated. The level of expression of CD25 (IL-2 receptor) was similar in patients and controls before and after 24 h stimulation with PHA. We conclude that there is a disturbance in the functional properties of peripheral blood T cells that can contribute to the immunopathogenesis of SS. Meanwhile, the quantitative reduction of suppressor/inducer lymphocytes as defined by the CD4 2H4 phenotype can be precluded from a role in the development of such an autoimmune condition. | |
| 7481480 | An immunohistochemical study of immunological phenomena in minor salivary glands in patien | 1995 | Using different monoclonal antibodies, we performed an immunofluorescent technique on labial salivary glands in order to investigate the immunological phenomena involved in Sjögren's syndrome (SS). An aberrant expression of HLA-DR molecules was detected on cytoplasm of epithelial labial salivary cells in 9 out of 19 (47%) patients, with SS. No such expression was found in 8 patients without SS or in 3 normal controls. HLA-DQ molecules were demonstrated also in two out of ten SS patients without HLA-DR. A lymphocytic infiltration was not correlated with the expression of class II molecules. T cells bearing gamma delta receptors were not detected. The intracellular adhesion molecules (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1) were not found on epithelial glandular salivary cells of patients and controls. In conclusion, these data suggested that the absence of ICAM-1 and LFA-1 in salivary cells and the absence of infiltrating T cells bearing gamma delta receptors exclude their immunopathogenetic role in SS; moreover, these data demonstrated that the aberrant expression of HLA class II molecules on epithelial salivary cells of patients with SS is not a phenomenon correlated with the lymphocytic infiltration. | |
| 8242827 | [Lymphocyte subsets in labial salivary gland of Sjogren's syndrome]. | 1993 Apr | Using the immunohistochemical avidin-biotin-peroxidase complex (ABC) method, lymphocyte subsets in the salivary glands of 15 patients with primary Sjogren's syndrome, 7 patients with secondary Sjogren's syndrome and 4 normal controls were identified by monoclonal antibodies. The infiltrating lymphocytes were mainly T lymphocytes, the majority of which were T helper cells (Leu-3a) in SS groups. The Leu-3a/Leu-2a ratio was increased. These changes were related to the degrees of the disease. The lymphocytes of patients expressed the HLA-DR antigen (Ia). Thus genetic predisposition plays an important role in the disease. A proposed mechanism is that the deficiency of suppressor lymphocytes and the overactivity of helper lymphocytes would result in B cells becoming hyperactive. Multiple autoantibodies produced by the B cells would contribute to tissue damage, and the tissue fragments would in turn further stimulate antibody production. | |
| 8339139 | The association of HLA DR beta alleles with self-limiting and persistent forms of early sy | 1993 Jul | RA is associated with a group of class II DR beta alleles, which share a conserved sequence in the third allelic hypervariable region (3AHVR). These include the DR4 subtypes Dw4, Dw14 and Dw15, and also DR1. In contrast Dw10 and Dw13 which are also DR4 subtypes show no association with RA and have a quite distinct 3AHVR. We have assessed the frequency of these alleles in 55 patients who initially presented with symmetrical peripheral polyarthritis suggestive of RA. After 4 years 27 had progressed to definite or classical RA, while 28 had never fulfilled the criteria for this disease. Dw4 was markedly elevated in the rheumatoid group (17/23) compared with either the non-rheumatoids (5/28) or healthy controls (12/100). Dw14 and non-DR4 associated DR1 were not elevated in either group of patients. This study suggests that the DR beta association with RA is likely to facilitate persistence or severity of disease rather than the initial induction of symmetrical peripheral arthritis. | |
| 1503637 | Inhibition of T cell activation by MHC blockade: a possible strategy for immunointerventio | 1992 Apr | Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on blockade of MHC class II molecules in the treatment of HLA-linked autoimmune diseases. | |
| 8812700 | Activation of T Cells by Autoantigen Immobilized by Specific Antibodies. | 1996 Jun | A convenient microtiter-plate assay that uses immobilized antibody to capture specific antigens for presentation to T cells has been developed. Initial experiments used KLH as the antigen, immune antisera and draining lymph node cells from immunized NOD mice as the source of antibody and T cells, and spleen cells from naive NOD mice as the source of antigen-presenting cells (APCs). The resulting proliferation of the T cells was shown to be antibody- and antigen-specific, suggesting that the APCs had internalized and processed the captured antigen, presenting it to the T cells in the form of peptide/MHC complexes. The approach was also tested for an autoimmune disease as part of an effort to identify autoantigens responsible for the proliferation of T cells in the synovial fluid of rheumatoid arthritis patients. When immunoglobulin from autologous synovial fluid was captured on plates coated with anti-human immunoglobulin antibodies, the addition of HLA-DR4 peripheral blood mononuclear cells as APCs and synovial fluid-reactive HLA-DR4-restricted T-cell clones resulted in significant proliferation, indicating that the specific antigen in the crude synovial fluid was human immunoglobulin. This response was also shown to be antigen-specific and HLA-DR4-restricted. This assay format should permit the definition of autoantigens by capturing with antibodies to crude autoantigen extracts, followed by the addition of the appropriate APC and T-cell populations. | |
| 8781716 | Immunoglobulin allotypes (GM and KM) and their interactions with HLA antigens in autoimmun | 1995 | GM and KM immunoglobulin (Ig) allotypes and their interactions with HLA antigens have been analyzed in various autoimmune diseases: multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, coeliac disease, Crohn's disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. This review reports published results about associations or linkages, as well as the origins of the populations, the numbers of patients and controls tested. The possible role of Ig polymorphisms in the physiopathology of autoimmune diseases is discussed. Ig allotypes and statistical methods used to analyse the HLA and Ig data are also described. | |
| 7980711 | Lp(a) lipoprotein in cardiovascular disease. | 1994 Aug | The article summarizes the increased knowledge about the enigmatic Lp(a) lipoprotein and its clinical importance over the past 20 years. The mode of inheritance, the unique features of Lp(a) composition and structure and the unusual distribution of the mainly genetically determined plasma Lp(a) levels are discussed. The main factors that can significantly change the inherited plasma Lp(a) levels are endocrine disorders and hormone treatment. It seems possible that sex hormones protect females to a large extent from the potentially deleterious effects of inherited high Lp(a) levels until menopause. The exceptionally strong independent association found in most studies between Lp(a) lipoprotein levels and atherosclerotic disorders indicates that Lp(a) is a factor of outstanding importance in the pathogenesis of atherosclerosis. Probable pathogenetic mechanisms are reviewed. The associations found between LP(a) and insulin release, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms. In a new hypothesis it is suggested that an autoimmune process might especially occur in individuals with inherited high Lp(a) levels and certain HLA class II genotypes, triggered by a concurrent infection. | |
| 8151573 | Class II alleles in juvenile arthritis in Czech children. | 1994 Jan | OBJECTIVE: Patients with pauciarticular and polyarticular onset rheumatoid factor (RF) negative juvenile arthritis (JA) have been reported to have a variety of HLA associations. The reason for the differences found in several recent studies is not known. We compare a new series of patients investigated in Prague, Czechoslovakia with those we reported from Dallas. METHODS: Czech patients with JA (N = 153) were classified clinically using the same criteria as in our studies in Dallas. The RF negative group included 56 patients that had persistent pauciarticular disease, 42 pauciarticular with polyarticular course and 39 with polyarticular onset. RF was present in 13 additional patients. HLA class II alleles were determined by oligotyping as previously described from our laboratory. RESULTS: DRB1*0801 was increased and DRB1*0701 was decreased in all the RF negative groups. The persistent pauciarticular group was associated with DRB1*11 and DPB1*0201 and lacked the association with DRB1*1301 seen in Dallas. Also found in Prague and not in Dallas were an increase in the frequency of DR2 in pauciarticular patients with early conversion and of DRB1*1201 in patients with iritis. Certain HLA associations (DRB1*0801, DPB1*0201) appear to be present in patients with JA in most studies; others (DRB1*1301, DPB1*0301) are more variable. CONCLUSION: The reason for differences in the HLA risk factors observed in our 2 populations is not known. Clinical heterogeneity not detected by our method seems the most likely explanation. Genetic and environmental factors may also play a role. | |
| 8817167 | Epitope mapping of the Ro/SSA60KD autoantigen reveals disease-specific antibody-binding pr | 1996 Jun | Anti-Ro60KD autoantibodies are commonly found in sera from patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). In order to identify the epitopes of this autoantigen, 22-mer, synthetic peptides overlapping by eight residues, and covering the entire sequence of the Ro60KD autoantigen were prepared. Three groups of sera were evaluated according to their autoantibody specificites. The first group consisted of monospecific anti Ro60KD sera from four patients with SLE and one with SS, the second one was composed of anti-Ro60KD+anti-La(SSB)-positive sera from four patients with SS and the third group included three normal sera and one anti Ro52KD serum. It was found that sera from SLE patients interact with a common antigenic site spanning the sequence TKYKQRNGWSHKDLLRSHLKP (169-190) of the Ro60KD protein. On the other hand, sera from SS patients recognise the ELYKEKALSVETEKLLKYLEAV (211-232) region of this autoantigen. Determination of the minimal required peptide length for optimal antibody recognition showed that the defined epitopes can be shortened to the NGWSHKDLLR (175-184) and KALSVETEKLLKYLEAV (216-232) sequences respectively. Inhibition experiments using the Ro60KD antigen and soluble peptides corresponding to the 175-184 and 216-232 segments further confirmed the specific antibody binding. These results, although only a small number of sera were used, indicate that the Ro60KD autoantigen, which is not characterized by disease specificity, contains two discrete epitopes specifically recognized from SLE and SS patient sera. Finally, the sequence similarity of the NGWSHKDLLR (175-184) epitope with some of the HLA haplotypes, associated with anti-Ro response, deserves to be noted. | |
| 8305809 | Comparison of serological tests for the detection of antibodies against Chlamydia trachoma | 1993 Nov | In cases of reactive arthritis, a suspected Chlamydia trachomatis infection is often detected by serological methods. However, mostly tests with genus-specific antigens are used, neglecting the fact that antibodies against Chlamydia pneumoniae are highly prevalent in the adult population. Therefore we tested sera of 129 patients with various rheumatological disorders and of 18 healthy persons in parallel with a genus-specific test (IPAZYME) and with the species-specific microimmunofluorescence test for C. trachomatis and C. pneumoniae antibodies. The data showed that 55% of the 64 IPA-positive results were caused by antibodies (IgG) against Chlamydia pneumoniae, only 6% by anti-Chlamydia trachomatis IgG and 20% by both specificities. For IgA antibodies, the percentages were 44%, 12.5% and 12.5% respectively. In 12 IPA-positive cases, the MIF showed no reaction. 58% of all 147 sera tested with MIF had IgG antibodies against C. pneumoniae, 5% had anti-C. trachomatis IgG and 8% IgG against both species. The percentages for IgA were 29%, 2% and 2%, respectively. IgM positivity in MIF disappeared after absorption with rheumatoid factor absorbent. No significant differences were found between the various groups of patients. The data suggest that due to the high prevalence of anti-C. pneumoniae antibody, genus-species tests cannot be used as screening tests for the serological diagnosis of C. trachomatis infections. | |
| 8188366 | Mycoplasma arthritidis-derived superantigen induces proinflammatory monokine gene expressi | 1994 Jun | Soluble factors produced by Mycoplasma arthritidis play an important role in the pathology of arthritis in rodents, which closely resembles human rheumatoid arthritis. At least one of the products of these microorganisms, M. arthritidis-T cell mitogen (MAM), has biological activities in common with superantigens. These superantigens activate T cells in a V beta-restricted fashion, and this response is strictly dependent on the presence of major histocompatibility complex (MHC) class II-positive cells. In the present study, we have examined the ability of MAM to induce proinflammatory monokine (interleukin 1 beta [IL-1 beta] and tumor necrosis factor alpha [TNF-alpha]) gene expression in the THP-1 monocytic cell line. Treatment of these cells (which express a very low level of HLA-DR molecules) with gamma interferon (INF-gamma) induced HLA-DR, -DQ, and -DP molecules and enabled them to respond to MAM in a dose-dependent manner, resulting in an increase in the level of steady-state mRNA for IL-1 beta and TNF-alpha. Stimulation of the U937 monocytic cell line (MHC class II-negative even after INF-gamma treatment) with MAM did not induce either IL-1 beta or TNF-alpha transcription. Moreover, MAM adsorption on Raji (MHC class II-positive) cells resulted in the loss of its cytokine-inducing activity to induce monokine gene expression. These findings demonstrate clearly that MAM induces monokine gene expression following interaction with MHC class II molecules. Pretreatment of INF-gamma-treated THP-1 cells with the transcription inhibitor actinomycin D prevented the induction of monokine mRNA, whereas cycloheximide superinduced mRNA after stimulation with MAM. Finally, our results, obtained with protein tyrosine kinase inhibitors and antiphosphotyrosine Western blotting (immunoblotting), indicate that protein tyrosine kinase is involved in MAM-induced IL-1 beta and TNF-alpha gene expression in the THP-1 monocytic cell line. The capacity of MAM to induce proinflammatory cytokine transcription in monocytes via MHC class II molecules can be one pathway of MAM contribution to autoimmune diseases. | |
| 7587736 | Comparison of monoclonal antibodies for flow cytometric analysis of HLA-B27 antigen. | 1995 Mar 15 | HLA-B27 is an antigen associated with the disease ankylosing spondylitis. Ninety percent of Caucasians with ankylosing spondylitis possess the HLA-B27 antigen. However, only 20% of Caucasians with the HLA-B27 antigen will develop the disease. Defining the presence or absence of the HLA-B27 antigen can be helpful in differentiating ankylosing spondylitis from juvenile rheumatoid arthritis. In this study, we evaluated the application of two monoclonal antibodies (MoAbs), using flow cytometric analysis for the detection of HLA-B27 antigen. After an initial comparison of HLA-B27 analysis by flow cytometry to the standard microlymphocytotoxicity assay, cutoffs were established to differentiate HLA-B27 positive from HLA-B27 negative. One MoAb showed very reliable results with > 99% accuracy in discriminating HLA-B27 positive from HLA-B27 negative samples. Various parameters were investigated to obtain the optimum results and showed that incubation time, reagent lot, and the flow cytometric instrument can affect the results. We concluded that a reliable MoAb and flow cytometry are valuable for the rapid and inexpensive determination of HLA-B27 typing in the clinical setting. However, testing conditions can affect the accuracy of results; therefore, adequate parallel testing in various conditions must be performed in order to establish the proper standards. | |
| 8251150 | Autoimmunity in schizophrenia: a review of recent findings. | 1993 Oct | The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed. | |
| 8952665 | [Cutaneous reactions to gold salts]. | 1996 Oct 26 | Gold salts are used for rheumatoid arthritis, and also in resistant corticosteroid dermatoses such as pemphigus. Gold salts inhibit the expression of endothelial cell adhesion molecules, but activity varies from one molecule to another; thiomalate alone gives the same effect. Patients given gold salts have as high risk of cutaneous reactions, and a provisional diagnosis of "gold dermatisis" is insufficient. The mechanisms of cutaneous reactions are unknown and vary according to the molecules. Smokers, HLA Bw35 patients and perhaps atopic states are more prone to gold drug reaction. Inflammation at the site of injections is frequent but with no consequence. Accumulation (chrysiasis) may be observed with long-term treatment. The main problem is its diagnosis as it may mimic numerous dermatoses. Immunological adverse events are the most frequently encountered. Pruritus is frequently observed, more often with oral salts. Exanthemas are common and may disclose an associated visceral disease. Drug hypersensitivity is rare, but severe. All these types necessitate drug interruption although prescription has been continued after development of pityriasis rosea-like and eczematous eruptions in some series without worsening. Lichenoid eruptions require withdrawal, but the skin disease may continue. Oral presentation is frequent, either as a taste abnormality, or as stomatitis. Contact dermatitis may flare in patients sensitized to gold. Rare non-immunological skin diseases have been also observed. Careful dermatological assessment correlated with an imputability method and search of visceral side-effects could lead to a better choice for the patient. Skin tests are not reliable. | |
| 1355612 | Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via the CD2 m | 1992 Sep | Only a minority of T cells at cell-mediated immune lesions are antigen specific. In the lesions of human autoimmune disease, such as the synovial membrane in rheumatoid arthritis, the T cells are activated as shown by a variety of phenotypic and functional changes including the expression of HLA-DR and the production of interleukin-6 (IL-6). The stimulatory pathway involved is unknown but does not seem to involve the T-cell receptor. Alternative pathways of activation which may be involved include the CD2 molecule. It is shown that the formation of sheep red blood cell (SRBC) rosettes with resting T cells from human peripheral blood, which is equivalent to CD2/LFA-3 binding, leads to the de novo transcription of the HLA-DR and IL-6 genes and the expression of HLA-DR on the surface of the T cells. There was no transcription of the interleukin-2 (IL-2) or the interleukin-2 receptor (IL-2R) genes and Tac expression was not seen. The rosetted T cells did not proliferate. These are all characteristics of T cells at chronic inflammatory sites. It is concluded that receptor-ligand interactions between CD2/LFA-3, which are expressed in increased amounts in the rheumatoid joint, may be one pathway by which antigen non-specific T cells are recruited as effector cells in lesions of human autoimmune disease. |