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The purpose of this study was to investigate interleukin 2 (IL-2) and gamma interferon (IFN-γ) production by purified CD4+ and CD8+ cells isolated from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and other inflammatory arthritides (non- RA). CD4+ and CD8+ cells were selected positively by immunomagnetic separation, Supernatants of unstimulated CD4+ and CD8+ cells from both compartments did not contain any detectable IL-2 or IFN-γ while supernatants of CD4+ and CD8+ cells stimulated with phytohaemagglutinin and irradiated Raji cells mostly contained both cytokines. In vitro stimulated SF CD4+ cells gave supernatants with significantly less IL-2 than supernatants from PB CD4+ cells, while in vitro stimulated SF CD4+ -cell supernatants contained significantly more IFN-γ. SF CD4+ -cell supernatants contained significantly more IL-2 than the parallel CD+ supernatants, while there was no significant difference with regard to IFN-γ content. The pattern of differences between SF-and PB-derived T cells was the same for the two groups of patients, but the SF CD4+ cells from RA patients produced significantly less IL-2 than the corresponding cells from the non-RA group. The difference between SF and PB T cells with regard to lymphokine production is probably related to various degrees of in vivo pre-activation. The results do not indicate a major T-cell deficiency in relation lo lymphokine production in RA. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to study purified synovial fluid (SF) CD4+ and CD8+ cells from patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (non-RA) with respect to the proliferative response to mitogens and recombinant interleukin 2 (rlL-2). Highly purified cell subsets were isolated by an immunomagnetic technique, and spontaneous proliferation as well as proliferative responses to rIL-2 and a combination of phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) (to substitute for accessory cells) were measured. Some patients had SF CD4+ and/or CD8+ cells with moderately increased spontaneous proliferation, but only the CD4+ cells of the two patient groups differed significantly from the peripheral blood (PB) T-cell subsets of healthy individuals who served as controls. The response to rlL-2 was variable but generally low, although about 50% of the CD4+ and 20% of the SFCD8+ cells of both patient groups expressed the Tac antigen. The response to PHA/PMA was significantly lower for RA SF CD4+ cells than for non-RA SFCD4+ cells, which again was lower than for normal PB CD4+ cells. SF CD8+ response to PMA/PHA by both groups of patients was somewhat decreased, but not significantly lower than in the controls. Thus, the CD4+ cells seemed functionally more deviant than the CD8+ cells in both patient groups, but the abnormality was most pronounced in the RA group. The results demonstrate that the previously reported diminished response to mitogens by SF mononuclear cells is present even when SF CD4+ cells are cultured alone. This indicates that these T cells have a reduced response, probably because of prior activation. [ABSTRACT FROM AUTHOR]

We studied the expression of the Tac antigen, the transferrin receptor (Tfr-R), HLA class II antigens (DR, DQ, DP), CD30, and Act 1 on purified CD4+ and CD8+ cells isolated from synovial fluid (SF) synovial tissue (ST), and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and with non-RA inflammatory arthritides (not ST). Subfractionated T cells of PB from healthy individuals served as controls, SF CD4+ cells from RA and non-RA arthritides expressed the Tac antigen much more frequently than corresponding CD8+ cells (54 and 58% versus 16 and 17%). In contrast, SF CD8+ cells of both patient groups expressed the HLA class II antigens rather more frequently than the corresponding CD4+ cells (88 and 68% versus 72 and 40%). Tfr-R expression was low on CD4+ and CD8+ SF T cells from both patient groups, SF T cells did not express CD30, and their expression of Act 1 did not differ from that of normal PB T cells. The RA ST findings were similar to those of RA SF. The overall expression of activation markers on PB T cells of patients was slightly higher than on those of normal controls, and the RA group was slightly higher than the non-RA group. The results show that intra-articular T cells in arthritis are activated and that CD4+ and CD8+ subsets differ in their expression of Tac antigen and HLA class II antigens. There were also similar patterns of activation markers on both CD4+ and CD8+ SF cells from RA and non-RA arthritis patients, suggesting that several types of arthritis display a similar immunopathogenesis in the joints. [ABSTRACT FROM AUTHOR]

Since there have been conflicting findings about the presence of interleukin 2 (IL-2) in synovial fluid (SF) of patients with rheumatoid arthritis (RA), we decided to study this subject ourselves, In a sensitive assay utilizing CTLL-2 as indicator cells, no IL-2-like activity was found in SF from any of the 15 RA patients studied. Treatment of SF with hyaluronidase, dialysation, heating to 56°C for 1 h, preincubation of CTLL-2 with SF prior to washing and incubation all resulted in no detection of any IL-2. SF itself did not inhibit the CTLL-2 assay. Failure to detect IL-2 may to some extent be explained by in vivo absorption of any IL-2 by IL-2 receptorpositive T cells in SF. The failure is discussed along with new evidence from various reports suggesting that impaired IL-2 production by activated T cells may be a feature of several autoimmune diseases. [ABSTRACT FROM AUTHOR]

We have studied the immunoregulatory function of T8+ (suppressor/cytotoxic) and Leu3a+ (inducer/helper) T cells from rheumatoid arthritis (RA) patients by measuring the effect of these T-cell subpopulations on the generation of immunoglobulin-secreting cells by normal allogeneic B cells after stimulation with pokeweed mitogen (PWM) in vitro. When T8+ or Leu3a+ cells from blood or synovial tissue from nine patients were substituted for T8+ or Leu3a+ cells, respectively, from normal blood mononuclear cells (MNC), RA T8+ cells showed an increased suppressor activity, whereas RA Leu3a+ cells were, except for one patient, weak augmentors. Unreplaced normal MNC and MNC replaced with allogeneic normal T-cell subpopulations responded equally to PWM. When T8+ plus Leu3a+ cells from the same patient replaced normal T cells, high B-cell responses were detected. Normal T8+ plus Leu3a+ cells generally supported the response to a lower degree. Substitution with two allogeneic T-cell subpopulations did not result in a B-cell response to PWM. Thus, whereas RA T8+ seemed to be strong suppressors and RA Leu3a+ cells weak augmentors by themselves, together they are possibly able to generate a B-cell stimulatory potential that might be of pathogenetic significance in the patients. [ABSTRACT FROM AUTHOR]

Mononuclear cells (MNC) eluted from rheumatoid synovial tissue of 16 patients with rheumatoid arthritis were examined for immunoglolulin-secreting cells (ISC). Immediately after elution and separation synovial tissue MNC contained considerable numbers of ISC. IgG and IgA ISC were more abundant than IgM ISC. At the same time there were low numbers of ISC in blood. Synovial tissue ISC were lost during incubation with pokeweek mitogen (PWM), possibly because tissue MNC were already maximally triggered in vivo. This was in contrast to blood MNC, in which the number of ISC increased significantly during incubation with PWM. [ABSTRACT FROM AUTHOR]

The lymphocyte responses in autologous mixed lymphocyte reactions (AMLR) between irradiated non-T and T lymphocytes from the peripheral blood (PB) of rheumatoid arthritis (RA) and juvenile RA (JRA) patients were decreased compared with the AMLR responses of normal PB lymphocytes. Normal AMLR responses were seen in the synovial tissue and the synovial fluid lymphocytes from RA and JRA patients. The lymphocyte responses were also decreased in AMLR between irradiated non-T cells from peripheral blood and T cells from synovial tissue (ST) in RA patients and between irradiated non-T from PB and synovial fluid (SF) T cells in JRA patients. However, when irradiated non-T cells from ST of RA patients or from SF of JRA patients were mixed with autologous PB T lymphocytes, increased lymphocyte responses wore observed. SF T lymphocyters and ST T cells were also shown to stimulate autologous PB T lymphocytes. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies with specificities for various human T-cell antigens were used in direct immunofluorescence to quantify the proportions of T lymphocytes with suppressor/cytotoxic-cell markers and with helper/inducer-cell markers and of T lymphocytes with HLA-D R antigens. Normal percentages of lymphocytes with suppressor/cytotoxic-cell markers were detected in the peripheral blood synovial fluid and synovial tissue lymphocytes from patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA), respectively. Normal percentages of T lymphocytes with helper/inducer-cell markers were seen in the peripheral blood of RA and JRA patients and in the synovial tissues of RA patients. Slightly decreased percentages of cells with the helper/inducer-cell marker were detected in the synovial fluids of JRA patients. The proportions of HLA-DR-positive T lymphocytes were highly increased in the synovial fluid and synovial tissue, whereas the numbers of these cells in the peripheral blood were normal. No significant differences in Tγ cells were detected between peripheral blood, synovial fluid and synovial tissue of JRA patients or between peripheral blood and synovial tissue of RA patients. [ABSTRACT FROM AUTHOR]