Rheumatoid Inflammatory T‐Cell Clones express mostly Th1 but also Th2 and Mixed (Th0‐Like) Cytokine Patterns

Abstract

This study was performed in order to characterize whether T cells from rheumatoid synovial inflammation belong to the Th1- or Th2-like functional subsets. Cytokine production was studied in 26 CD4+ alpha beta+ and 2 CD8+ alpha beta T-cell clones from the synovial fluid, the synovial membrane and peripheral blood of 5 patients. Fifteen of the CD4+ clones were raised against various mycobacterial antigens and 11 CD4+ clones and 2 CD8+ clones were raised unspecifically using PHA and/or IL-2. The specificities of these clones are not known. In the mycobacterial antigen-specific group, all CD4+ alpha beta T-cell clones produced IFN-gamma at high levels, while the production of IL-4 was generally absent or low (< 1 ng/ml), consistent with a Th1-like profile. Some of these clones, however, also produced various amounts of IL-10 which has been regarded as a Th2 product but can be produced also in lower amounts by Th1 cells. One HSP-65-specific clone produced levels of IL-4 and IL-10 in the same order as that of IFN-gamma, thus appearing to be Th0-like. Among the 11 unspecific CD4+ clones, 7 showed a Th1-like pattern but with lower levels of IFN-gamma than the antigen-specific clones. However, three clones did not produce any IFN-gamma activity but produced IL-4 and one of them also produced distinct amounts of IL-10, compatible with a Th2-like pattern. In addition, one of the clones also showed an almost equally strong IFN-gamma and IL-4 production, thus most likely representing a Th0-like clone.

Differential effects of interleukins 10 and 4 on the production of interleukin‐6 by blood and synovium monocytes in rheumatoid arthritis

“…As for IL-10, these T lymphokines were virtually undetectable in the supernatants of undigested RA synovium (28). These results suggest that the regulatory effect of IL-4 and IFNy on IL-I0 production observed in vitro could have occurred locally in vivo, since d p and y/S RA T cell clones produced large amounts of IFNy and no or low levels of IL-4 and IL-10 in vitro (29,30). Taken together, these results suggest the REGULATION OF IL-6 PRODUCTION BY presence of a regulatory balance at work inside the synovium, where the local production of IFNy may limit the antiinflammatory properties of IL-10, thus leading to disease perpetuation.…”

Switch in Chemokine Receptor Phenotype on Memory T Cells without a Change in the Cytokine Phenotype

“…T cells expressing high levels of CCR3 were found in only two out of the 14 patients analyzed. As such, the chemokine receptor phenotype of our T cells correlates with the usual IFN-g-producing Th1 type in RA tissue [17]. Since CCR5 and CCR3 are downregulated during the activation and proliferation process and is not re-expressed until the effector stage is reached [30], the expression of CCR5 and CCR3 was analyzed when the T cells had ended their proliferation stage.…”

“…In RA a large number of lymphocytes infiltrate the joint where a chronic inflammation occurs [16±18]. T lymphocytes in the RA synovium are predominantly memory cells of Th1 type, defined by mRNA expression and their in vitro production of IFN-g [7,17,19]. It has been suggested that a shift in the cytokine balance in RA could have a beneficial effect [20].…”

Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype

“…The latter issue has been addressed in a few studies which have shown a predominant Th1 pattern in synovial membrane [18][19][20][21] or fluid [19] T cells from rheumatoid arthritis (RA) patients. Virtually no information is available on the patterns of cytokine production by synovial T cells from children with JA, in particular with the oligoarticular subtype.…”