Michael J. Dauphinée

Deficient T-cell mitogen response in murine experimental autoimmune myasthenia gravis: A defect in the adherent cell population

T-Lymphocyte number and functions are often reduced, while B-lymphocyte function is often increased in patients with autoimmune disorders. To study the mechanisms responsible for these T-cell malfunctions in autoimmunity we adapted the murine experimental autoimmune myasthenia gravis (EAMG) model. Splenocytes from C57BL/6 mice immunized with acetylcholine receptors (AChR) in complete Freunds adjuvant (CFA) produced approximately half the amount of concanavalin A (Con A)-induced interleukin 2 (IL-2) as did splenocytes of CFA-inoculated controls. Further, AChR plus CFA-immunized splenocytes showed a marked reduction in T-cell proliferative responses induced by Con A or phytohemagglutinin when compared with CFA-inoculated controls. By contrast, lipopolysaccharide-induced B-cell function is preserved. Deficient Con A splenic T-cell response is seen early after secondary inoculation with CFA or AChR in CFA. T-Cell recovery occurs in CFA-inoculated mice but not in AChR plus CFA-inoculated mice. Defective Con A splenic T-cell response seen early after secondary immunization with CFA or AChR in CFA is due to the presence of a defective splenic adherent cell population. Moreover, defective Con A splenic T-cell response seen after established autoimmunity to AChR in EAMG is also due to the presence of a defective splenic adherent cell population.

Characterization of the IL-2-receptor on rheumatoid arthritis synovial fluid T cells

We studied the hypoproliferative response of synovial fluid (SF) T cells in rheumatoid arthritis (RA) using a mitogenic monoclonal antibody (MoAb) specific for the T-cell antigen receptor-associated CD3 complex. RASF T cells are defective in their proliferative response and in the induction of the Tac (p55) component of the IL-2-receptor (IL-2-R) when stimulated with anti-CD3 monoclonal antibody (MoAb). However, fresh RASF T cells bear demonstrable IL-2-R in cross-linking experiments which are not seen in unstimulated peripheral blood (PB). These receptors are functional since RASF T cells proliferate in response to recombinant IL-2 (rIL-2) better than fresh PB T cells from either normal or RA patients. Scatchard analysis indicates increased (4-fold) numbers of high affinity IL-2-R on (phytohaemagglutinin) PHA-activated RASF T cells as compared with comparably activated RAPB T cells. Phorbol myristate acetate (PMA) induces Tac antigen expression in RASF but does not lead to proliferation. The hyporesponsiveness of RASF T cells does not appear to result from lack of IL-2-R, lack of IL-2-R inducibility, or proliferative potential.