Glucocorticosteroids modulate antigen-induced T cell apoptosis in experimental autoimmune neuritis and cause T cell proliferation in situ

Treatment of experimental autoimmune disorders of the nervous system with h igh doses of glucocorticosteroids (GC) or with administration of the specif ic antigen is effective and associated with marked T cell apoptosis in situ . Here we investigated in adoptive transfer-experimental autoimmune neuriti s (AT-EAN) of the Lewis rat whether induction of T cell apoptosis resulting from T cell activation by antigen therapy can be further augmented by gluc ocorticosteroids (GC). AT-EAN was induced by intravenous injection of P2-sp ecific T cell blasts. At the maximum of disease two pulses of the antigen r ecombinant human P2 (rhP2) were given within 12 h. Methylprednisolone was a dministered simultaneously or 2 h after the antigen and animals were killed 6 h after the second antigen injection. Using an in situ tailing technique followed by immunocytochemical analysis, the presence of DNA fragmentation in T lymphocytes was confirmed. The bromodeoxyuridine (BrdU) technique was employed to detect in situ proliferating cells. T cell apoptosis in sciati c nerve was enhanced after monotherapy with either antigen or GC compared t o the control group receiving an irrelevant myelin protein, recombinant hum an PO. In combination therapy, a synergistic effect on T cell apoptosis in sciatic nerve was obtained when methylprednisolone was injected sequentiall y, 2 h after rhP2 protein. BrdU incorporation in the sciatic nerve as well as in the spleen, a major lymphoid organ, was significantly enhanced in ani mals treated with antigen followed by GC 2 h later as compared to rats rece iving rhP2 only, speaking for T cell proliferation in situ associated with T cells undergoing apoptosis. Our findings underscore that different proapo ptotic stimuli may act synergistically, depending on the timing of the seco nd treatment. In this scenario even local T cell proliferation in the infla med nervous system occurs. These results support the paradigm of antigen pr esentation in the nervous system.