Augmented Numbers of HLA-DR-Positive T Lymphocytes in the Synovial Fluid and Synovial Tissue of Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis

Twenty to 40 % of T cells from synovial fluid and synovial tissue and 3–11 % of the peripheral blood T lymphocytes from patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) expressed HLA-DR antigens as detected by monoclonal anti-HLA-DR antibodies in direct immunofluorescence. Synovial fluid and synovial tissue T lymphocytes had a stimulating capacity comparable to that of non-T cells in the allogeneic primary mixed lymphocyte reaction (MLR). The MLR was inhibited by monoclonal anti-HLA-DR antibodies. This is, to our knowledge, the first report on in-vivo-activated T lymphocytes as stimulator cells in MLR. The results suggest that T cells from synovial fluid and synovial tissue are locally activated by stimuli so far unidentified.     

Detection of T-Lymphocyte Subpopulations in the Peripheral Blood and the Synovium of Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis Using Monoclonal Antibodies

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-DR 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 T gamma cells were detected between peripheral blood, synovial fluid and synovial tissue of JRA patients or between peripheral blood and synovial tissue of RA patients.     

Dendritic Cells from Human Rheumatoid Synovial Inflammatory Tissue and Peripheral Blood as Accessory Cells in Mitogen Stimulation of T Lymphocytes.

Dendritic cells (DC) were purified from the peripheral blood (PB) of normal individuals and from the synovial fluid (SF) and synovial tissue (ST) of patients with rheumatoid arthritis. These cells are strongly HLA-DR positive and lack B-cell, T-cell, and monocyte markers as well as Birbeck granules. The DC were compared with monocytes and non-T cells from PB for their ability to act as accessory cells for T-cell responses to concanavalin A (Con A) and phytohaemagglutinin (PHA). DC from PB, SF and ST were much more efficient accessory cells for the mitogenic responses than autologous monocytes from PB. The mean PHA responses in cpm obtained with DC from the various compartments were 4-20 times greater than the responses obtained with monocytes from PB. The Con A responses obtained when the various DC populations were used as accessory cells were 3-13 times greater than those obtained with monocytes from PB. The mitogenic responses seen with monocytes were very low. The non-T cells, which comprise a mixture of cells obtained after removal of T cells, also gave low T-cell responses to PHA and Con A compared with DC as accessory cells.     

In Vitro Mitogen Stimulation of Synovial Fluid Lymphocytes from Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis Patients: Dissociation between the Response to Antigens and Polyclonal Mitogens

The in vitro responses to mitogens of synovial fluid lymphocytes obtained from eight patients with rheumatoid arthritis (RA) and eight patients with juvenile rheumatoid arthritis (JRA) were studied. The results were compared to the transformation of the patient's peripheral blood lymphocytes stimulated with the same mitogens. Both RA and JRA synovial fluid lymphocytes showed a low transformation to the polyclonal mitogens PHA and PWM with a low ratio PHA-response/PWM-response. The stimulatory effect of purified protein derivative of tuberculin (PPD) was high, whereas a Candida albicans antigen preparation gave a more variable stimulation of the synovial fluid lymphocytes. In some patients the complete mitogen transformation profile of lymphocytes obtained from synovial fluid, synovial tissue and peripheral blood was studied. The results of the synovial fluid and tissue lymphocytes were similar.     

Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood.

Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA.     

Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells.

Earlier studies from this laboratory provided evidence for restricted cytokine expression in the T cell population in RA tissues. Specifically, IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) gene expression levels were low. The selective chemoattractant and activation effects of chemokines on leucocytes identify them as potentially ideal candidates in mediating selective inflammatory processes in RA. Accordingly, we undertook studies to examine constitutive chemokine gene expression in RA tissues. RANTES, monocyte chemotactic protein-1 (MCP-1) and MIP-1 beta gene expression was examined in both the T and non-T cell populations in RA peripheral blood (PB), synovial fluid (SF) and synovial tissues (ST). Our results identified elevated levels of both RANTES and MIP-1 beta gene expression in circulating RA PB and SF T cells. By contrast, MCP-1 expression was virtually absent in RA PB, yet elevated MCP-1 mRNA levels were detected primarily in the non-T cell populations of the SF and ST samples. Histological examination of affected rheumatoid joints revealed extensive RANTES and MIP-1 beta expression in sites of lymphocyte infiltration and cell proliferation, namely the synovial lining and sublining layers. Fractionation or RA ST patient samples revealed that RANTES expression was restricted to the T cells, whereas MIP-1 beta expression was detected in both T and non-T fractions. These data suggest that MCP-1, MIP-1 beta and RANTES may have a central role in the trafficking of reactive molecules involved in immunoregulation and in the inflammatory processes in RA.     

The distribution and functional properties of dendritic cells in patients with seronegative arthritis.

Dendritic cells (DC), potent antigen-presenting cells, are known to be increased in numbers in inflammatory lesions in rheumatoid arthritis and juvenile chronic arthritis. In this study, patients with seronegative arthritis were studied; the distribution and functional properties of DC enriched low density cells (LDC) from peripheral blood (PB) and synovial fluid (SF) were compared. The composition of LDC from both sources was similar, comprising approximately 30% DC, 60% monocytes with few T lymphocytes. SF was significantly enriched for LDC compared with paired peripheral blood (P less than 0.0001) or peripheral blood from healthy controls (P less than 0.001). In contrast, patient PB contained fewer LDC (P less than 0.05) overall than healthy controls. LDC from both sources were potent simulators of allogeneic PB T cells in a mixed leucocyte reaction (MLR), but in four out of 10 patients SF LDC were significantly more stimulatory. In autologous MLRs (AMLRs) SF T cells were not stimulated by either LDC population. This anergy of T cells was confined to the joint as patient PB T cells showed an AMLR response to PB LDC which was similar to that seen in cells from healthy controls. PB T cells also responded to SF LDC; in a minority of patients SF LDC caused significantly greater stimulation in AMLR than PB LDC and the possibility is discussed that this may represent presentation of antigen acquired in vivo.     

Activation of OKT4 suppressor cells in the autologous mixed lymphocyte reaction of patients with juvenile rheumatoid arthritis.

Activation of suppressor cells by the autologous mixed lymphocyte reaction (AMLR) was studied in patients with juvenile rheumatoid arthritis (JRA). Isolated OKT4 cells were used as responders and irradiated whole non-T cell preparations, non-adherent non-T cells (B and null cells), adherent non-T cells (monocytes), and B cells preactivated by Staphylococcus aureus Cowan I, as stimulators in the AMLR. Suppression was assessed by a reduction of pokeweed mitogen stimulated immunoglobulin synthesis by lymphocytes of healthy donors upon addition of AMLR-activated OKT4 cells. The results of this study suggest normal activation of OKT4 suppressor cells in the AMLR of patients with JRA.     

T-Cell Helper Activity and B-Cell Function of Synovial and Blood Lymphocytes from Patients with Rheumatoid Arthritis or Other Forms of Chronic Arthritis

The helper effect of T cells on B-cell immunoglobulin (Ig) responses induced by pokeweed mitogen (PWM) or purified protein derivative of tuberculin (PPD) was studied in lymphocytes from synovial fluid (SF) and blood of nine patients with rheumatoid arthritis (RA) and eight patients with other forms of chronic arthritis. In PWM cultures the helper effect of SF T cells on Ig responses (IgG, IgM, IgA) of autologous and allogeneic blood B cells was lower than that of blood T cells (P less than 0.01). This decrease was more pronounced in patients with RA than in patients with non-RA. In PPD cultures no significant difference was found between the helper effect of SF T cells and blood T cells on the Ig responses of allogeneic blood B cells or on the IgG response of autologous blood B cells, whereas the helper effect of SF T cells on the IgM and IgA responses of autologous blood B cells was decreased. The Ig responses to PWM or PPD in cocultures of autologous blood B and T cells were not significantly different between patients and healthy controls. The PWM- and PPD-induced Ig responses of SF B cells were lower than those of blood B cells when cocultured with autologous blood T cells. SF B cells produced IgG but usually little IgM and IgA. Thus there was a dysfunction of SF B cells and of SF T cells in a PWM-driven system, but a fairly good helper function of SF T cells in a PPD-driven system.     

Tγδ Cells in Juvenile Rheumatoid Arthritis and Rheumatoid Arthritis

Using the anti-TcRγ/δ-1 monoclonal antibody and flow cytometry, we examined the number of Tγδ cells in paired samples of peripheral blood and synovial fluid or tissue from 24 children with juvenile rheumatoid arthritis (JRA). five adult patients with JRA, and 14 patients with rheumatoid arthritis (RA). No significant difference was found in the synovial compartment Tγδ values compared with the blood in JRA, adult JRA, or RA patients. Nor was any significant difference found in the peripheral blood or synovial compartment Tγδ values in any of the three patient groups compared with the peripheral blood of normal controls. However, seven of the children with JRA had very high Tγδ values in the synovial compartment while none of the normal children had high Tγδ values in the blood (P= 0.02. Fisher's exact test). This may indicate a possible separate JRA patient group with high Tγδ levels in the synovial compartment. In six JRA patients further analysed for Tγδ subpopulations, a significant predominance of Vδ1 ⁺ cells was found in the synovial compartment compared with the corresponding peripheral blood samples (P<0 05. Wilcoxon's signed test) and with peripheral blood of child controls (P<0 05, Mann Whitney U test). In these six patients, the Tγδ -cell expression of the very early activation antigen CD69 were significantly higher (P<0 05. Wilcoxon's signed test) in the synovial compartment compared with the peripheral blood. Synovial Tγδ cells expressing HLA-DR and interleukin 2 receptors could also be detected, in contrast to the peripheral blood in which no Tγδ cells expressing these antigens could be found. These data suggest that the synovial Tγδ cells had been activated in vivo.     

Expression of Activation Antigens on T Cells in Rheumatoid Arthritis Patients

The aim of our study was to identify differences in cell surface marker expression between T cells taken from the peripheral blood (PB) of healthy individuals and T cells recovered from inflamed joints of rheumatoid arthritis (RA) patients. Out of 118 monoclonal antibodies (MoAbs) directed against activation antigens on haematopoietic cells, 12 MoAbs recognizing nine distinct surface molecules were selected after a screening procedure to study the expression of the corresponding antigens on T cells from the PB, synovial fluid and synovial tissue of RA patients, and also on T cells from PB and spleens of controls. Using two-colour flow cytometry and immunohistology we found the molecules B-C5, CD39, CD40, CD45 R0, CD54, CD76 and potentially 1D11 to be substantially up-regulated on T cells from various body compartments in RA patients. We thus could determine that the cell surface of T cells in RA patients not only differs in MHC class II expression, but also in a number of other activation-associated cell surface molecules from T cells in healthy individuals.     

CD44 Expression by Leucocytes in Rheumatoid Arthritis and Modulation by Specific Antibody: Implications for Lymphocyte Adhesion to Endothelial Cells and Synoviocytes In Vitro

Anti-CD44 MoAb IM7 induced the loss of CD44 from mouse leucocytes thereby inhibiting leucocyte migration and joint inflammation in murine arthritis. Thus, targeting CD44 with MoAb may have potential for the treatment of patients with inflammatory joint diseases. Expression of CD44 by peripheral blood (PB) and synovial fluid (SF) leucocytes from rheumatoid arthritis (RA) patients was compared and the ability of IM7 to modulate this expression determined. RASF lymphocytes showed increased CD44 expression compared with those in PB indicative of an activated phenotype. As inflammatory SF did not up-regulate CD44 expression on PB lymphocytes, the increased CD44 expression by SF lymphocytes was a result of the selective homing of CD44^high cells to the synovium rather than an effect of the synovial environment. RASF granulocytes showed reduced CD44 expression compared with those in PB, again indicative of an activated phenotype. However, this reduction could be induced on PB granulocytes following culture with inflammatory SF and was inhibited by anti-TNF-α MoAb, implying that soluble factors in inflammatory SF such as TNF-α induced granulocyte activation and CD44 loss. IM7 induced the loss of CD44 from lymphocytes (both from PB and SF) and granulocytes in vitro , but was subsequently re-expressed after 24 h culture in the absence of the MoAb. This loss of CD44 was blocked by serine- and metalloprotease inhibitors implying that IM7 induced the proteolytic cleavage of CD44 by a mechanism similar to that reported for the loss of CD44 from PMA-activated granulocytes. Furthermore, IM7-treated CD44^low lymphocytes showed reduced adherence to both an endothelial cell line and RA synovial fibroblasts in vitro . The unique ability of IM7 to reduce CD44 expression by lymphocytes suggests that it could prevent lymphocyte extravasation and synovial infiltration in RA as previously reported in murine arthritis.     

Modulation of Natural Killer Cell Activity in the Rheumatoid Joint and Peripheral Blood

Natural killer (NK) cell activity and its regulation in synovial fluid (SF). synovial tissue (ST). and peripheral blood (PB) was studied in 23 patients with active rheumatoid arthritis (RA). NK activity was reduced in PB (P< 0.005), SF (P <0.002), and ST of patients with RA compared to the PB of 28 healthy controls. NK activity in SF was inversely correlated wilh disease activity as measured by erythrocyte sedimentation rate (r=-0.561; P<0.02). Poly I:C. an Interferon inducer, stimulated NK activity in RA patients' PB and SF and control subjects' PB to similar extents. However, augmentation of NK activity by interleukin-2 was significantly greater in SF than in PB of RA (P<0.02). Preincubation of mononucleur cells with indomethacin significantly increased the NK activity of normal and RA PB but had no effect on that of SF. These observations suggest that the NK activity may be reduced in both PB and SF of RA and (hat functional differences between populations of cells with NK-like activity and/or differences in the control or modulation of NK activity exist between PB and SF.     

Immune Responses to 6 and 30-kDa Mycobacterial Antigens in Rheumatoid Patients, and Vβ Usage by Specific Synovial T-Cell Lines and Fresh T Cells

We have investigated both the humoral and the cellular immune responses of patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA) to mycobacterial antigens. The JRA group was not Bacillus Calmette Guerin (BCG) vaccinated whilst the majority of the RA group was. As determined by immunoblotting, 79% of sera from patients with JRA reacted mainly with a 18.6-kDa protein (P18.6), whilst 70% of sera from patients with RA reacted mainly with a 30-kDa protein (P30) of BCG, M. tuberculosis and M. kansasii. In contrast, only a moderate proportion of the control sera (25% of adult and 20% of children) showed reactivity to P30, and none of the samples had significant reactivity with the P18.6 antigen. Furthermore, T-cell proliferation to the P18.6 and P30 antigens was detected in the majority of JRA and RA patients, and was nearly always higher in synovial fluid (SF) than in the peripheral blood (PB). We also investigated the usage of V beta family genes in P18.6 and P30 antigen-specific T-cell lines established from the SF of one patient with active RA. We showed that V beta 2, -4, -5, -6, -7, -14, -17, -18 and V beta 19 were over-represented compared with other known V beta families. We also noted that the proportion of V beta 14 was higher in freshly isolated SF mononuclear cells compared with the blood in this patient and in 2 out of 4 other RA patients examined. Other V beta families such as V beta 6, V beta 8, V beta 16, V beta 18 and V beta 19 were also over-represented in the SF compared with the blood in some patients. Taken together our results provide more information concerning the role of mycobacterial antigens in RA and suggest that there may be an in vivo clonal expansion of T lymphocytes in the synovium.     

Expression of Activation Markers on CD4+ and CD8+ Cells from Synovial Fluid, Synovial Tissue, and Peripheral Blood of Patients with Inflammatory Arthritides

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.     

Characterization of Effector Memory CD8+ T Cells in the Synovial Fluid of Rheumatoid Arthritis

Little is known about the cellular characteristics of CD8(+) T cells in rheumatoid arthritis (RA). We addressed this by investigating whether the frequency of the CD8(+) T cell subsets and their phenotypic characteristics are altered in the peripheral blood and synovial fluid (SF) from patients with RA. In this study, CD8(+) T cells, mainly CD45RA(-) effector memory (EM) CD8(+) T cells, were increased significantly in the SF, but not in the peripheral blood from RA patients, compared with healthy controls. The synovial EM CD8(+) T cells were activated phenotypes with high levels of CD80, CD86, and PD-1, and had a proliferating signature in vivo upon Ki-67 staining, whereas the Fas-positive cells were prone to apoptosis. In addition, EM CD8(+) T cells in the SF were less cytotoxic, as they expressed less perforin and granzyme B. In particular, the proportions of synovial fluid mononuclear cells that were CCR4(+)CD8(+) T cells and IL-4-producing CD8(+) T cells (i.e., Tc2 cells) were significantly higher than those in peripheral blood mononuclear cells of patients with RA and healthy controls. In addition, the number of IL-10-producing CD8(+) suppressor T (Ts) cells increased significantly in the SF of RA patients. Especially, CD8(+) T cells were inversely correlated with disease activity. These findings strongly suggest that EM CD8(+) T cells in the SF are increased, likely because of inflammation, and they may be involved in modulating inflammation, thereby affecting the development and progression of RA.     

Autologous Mixed Lymphocyte Reaction in Man

Human peripheral T cells and T-cell Subpopulations defined with monoclonal antibodies of the OKT series were studied for the proliferative response on stimulation with autologous non-T cells or mitogen-activated T cells as stimulators in autologous mixed lymphocyte reaction (AMLR). T cells exhibited a vigorous proliferative response when stimulated with autologous non-T cells or activated T cells but not with unactivated T cells. The stimulatory capacity of non-T cells or activated T cells in AMLR was inhibited by prior treatment of stimulator cells with 7, 2 anti-human Ia framework-specific monoclonal antibody in the absence of complement. A BUdR and light technique was used to ablate proliferating T cells in response to either non-T cells or activated T cells in AMLR. The removal of T cells responding to autologous non-T cells left the responsiveness to autologous activated T cells relatively intact. Conversely, the removal of T cells responding to autologous activated T cells left the responsiveness 10 autologous non-T cells relatively intact. Thus T cells responding to autologous non-T cells appear to be distinct from those responding to autologous activated T cells in AMLR. Further analysis with OKT4 and OKT8 monoclonal antibodies showed that the major population responding to autologous non-T cells was contained in OKT4⁺ T cells and that responding to autologous activated-T cells was contained in OKT8⁺ T-cell subset. However, both OKT4⁺ and OKT8⁺ T-cell subsets responded by proliferation to non-T cells and activated T cells in allogeneic MLR. T cells selected after AMLR between T and non-T cells or T and activated T cells were treated with mitomycin and examined for their regulatory influence on the proliferative response of fresh autologous responder T cells. T cells selected from T and non-T AMLR augmented and those obtained from T and activated T AMLR suppressed the proliferative responses of fresh autologous T cells to phytohaemagglutinin and to autologous or allogeneic non-T cells in AMLR or allogeneic MLR. These findings indicate that in AMLR between T and non-T cells or T and activated T cells phenotypically distinct Subpopulations of T lymphocytes respond by proliferation and express distinct immunoregulatory functions.     

Con A-induced Suppressor Cell Activity and T-lymphocyte Subpopulations in Peripheral Blood Lymphocytes of Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis

Suppressor cell activity was investigated in peripheral blood lymphocytes from twenty patients with rheumatoid arthritis (RA) and twenty patients with juvenile rheumatoid arthritis (JRA) using a concanavalin A/mixed lymphocyte culture assay. The mean suppression in the RA patients was slightly reduced compared with the suppressor cell activity in adult controls (25 +/- 5% suppression compared with 37 +/- 5%; P less than 0.05, Student's t test), whereas the JRA patients had normal suppressor cell activity (mean 46 +/- 5% versus 43 +/- 5% in healthy children matched for age and sex). The RA patients had normal proportions of T-cell subpopulations, 13.3% T gamma cells and 49.8% T mu cells, compared with 13.8% and 58.0% in controls. The JRA patients, however, had a significantly reduced mean percentage of T gamma cells, 6.6%, compared with 13.8% in healthy children (P less than 0.05, Mann-Whitney U-test). The mean percentage of T mu cells was 53.7%, versus 56.2% in the controls. The relation between suppressor cell activity and suppressor cells enumerated by membrane markers is discussed.     

Immunoregulatory Function of T8 and T4 Cells from Synovial Fluid and Blood of Patients with Rheumatoid Arthritis or Other Forms of Chronic Arthritis

The suppressor effect of synovial fluid (SF) T8 cells and blood T8 cells on the pokeweed mitogen (PWM)-induced T4 cell-dependent immunoglobulin production of autologous blood B cells was studied in nine patients with chronic rheumatic diseases (six patients with rheumatoid arthritis (RA), one patient with juvenile RA, and two patients with other forms of chronic arthritis). The suppressor effect of SF T8 cells was of the same magnitude as that of equal numbers of blood T8 cells from patients and healthy controls. However, the relative number of T8 cells was higher among SF T cells than among blood T cells in several cases. Good synovial T8 cell suppression was also demonstrated in coculture experiments where SF T4 cells and B cells were used. In PPD (purified protein derivative of tuberculin)-stimulated cultures the suppressor effect of SF T8 cells as well as of blood T8 cells from patients and controls was lower than it was in PWM-stimulated cultures. In most patients SF T4 cells showed a much better PWM-induced helper function than did non-fractionated SF T cells. Thus the poor PWM induced helper effect of non fractionated synovial T cells was in some cases mainly due to the suppressor effect of T8 cells, whereas in some cases there was also a deficient helper function of synovial T4 cells.     

Impaired generation of high-affinity interleukin-2 receptors in the autologous mixed lymphocyte reaction in rheumatoid arthritis.

We examined the expression of high-affinity interleukin (IL)-2 receptors (IL-2R) as well as Tac and HLA-DR antigens on peripheral blood (PB) T cells from 11 rheumatoid arthritis (RA) patients and 8 healthy controls induced in the autologous mixed lymphocyte reaction (AMLR). The proportion of HLA-DR- and Tac-bearing T cells and expression of these activation antigens were higher in patients relative to controls (P less than 0.01) in freshly isolated unstimulated PB mononuclear cells. AMLR stimulation of RA T cells failed to induce an increase in the proportion of HLA-DR and Tac-bearing T cells which was observed in health controls. After AMLR stimulation the number of high-affinity IL-2R were significantly lower in RA patients compared with controls (P less than 0.01). The number of high-affinity IL-2R on patient T cells correlated strongly with AMLR reactivity as measured by [3H]thymidine incorporation (r = 0.821, P = 0.002). The results suggest that the AMLR defect in RA may result from impaired generation of high-affinity IL-2R.