- Paper Report
- Open Access
RA synoviocytes induce T cell anergy
- Sarah Parry1
© Current Science Ltd 2000
- Published: 24 October 2000
- synovial fbroblasts
- T cell anergy
Fibroblast-like synoviocytes (FLSs) in the rheumatoid synovial membrane (RA SM) show an activated phenotype with increased expression of MHC class II and adhesion molecules. It has been suggested that FLSs act as antigen presenting cells, and are involved in the activation of T cells. Within the RA SM, FLSs do not express CD80 or CD86 (B71 and B72), the classic ligands for CD28 and CTLA-4. Antigen presentation to T cells in the absence of a second signal may lead to T cell anergy, characterised by arrest at the G1 stage of the cell cycle with expression of the interleukin (IL)-2-receptor Î² chain CD25, but failure to produce IL-2. It has been shown that keratinocytes expressing MHC class II can induce short term anergy in this way (see Additional information). The authors investigated whether T cells within the RA SM are anergised by contact with FLSs. Specifically the authors investigated the phenotypic changes in FLSs and T cells co-cultured in either an autologous or an allogeneic in vitro system. They studied the functional effect of FLSs on T cells in the presence/absence of CD80, and tested whether primary contact with antigen presented by FLSs in the absence of CD80 costimulation induced T cell anergy.
Co-cultures of peripheral blood (PB) T cells with FLSs showed that activation markers are upregulated on both T cells (CD69, CD25) and FLSs (HLA-DR). Both PB T cells and RA synovial T cells showed reduced responses to allogeneic or recall antigen when co-cultured with FLSs. This reduced response could be normalised by including CD80-transfected fibroblasts in the co-cultures, indicating a role for CD80 in this system. Preculturing T cells with FLSs induced nonresponsiveness ('anergy') in both PB and RA synovial T cells tested in a two-stage culture protocol. Such nonresponsive T cells had three features suggestive of anergy: they failed to proliferate in secondary culture even in the presence of CD80, CD25 expression increased and proliferation could be restored by the addition of recombinant human IL-2.
In vitro co-culture and proliferation assays, FACS analysis, peripheral blood T cells, fibroblast-like synoviocytes
Otten HG, Bor B, Ververs C, Verdonck LF, De Boer M, De Gast GC
Alloantigen-specific T-cell anergy induced by human keratinocytes is abrogated upon loss of cell-cell contact. Immunology 1996, 88: 214-219.