Treatment of experimental
autoimmune disorders of the nervous system with high doses of glucocorticosteroids (GC) or with administration of the specific
antigen is effective and associated with marked T cell apoptosis in situ. Here we investigated in adoptive transfer-
experimental autoimmune neuritis (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 glucocorticosteroids (GC). AT-EAN was induced by
intravenous injection of P2-specific T cell blasts. At the maximum of disease two pulses of the
antigen recombinant human P2 (rhP2) were given within 12 h.
Methylprednisolone was administered 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 sciatic nerve was enhanced after monotherapy with either
antigen or GC compared to the control group receiving an irrelevant
myelin protein, recombinant human P0. In combination
therapy, a synergistic effect on T cell apoptosis in sciatic nerve was obtained when
methylprednisolone was injected sequentially, 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 animals treated with
antigen followed by GC 2 h later as compared to rats receiving rhP2 only, speaking for T cell proliferation in situ associated with T cells undergoing apoptosis. Our findings underscore that different proapoptotic stimuli may act synergistically, depending on the timing of the second treatment. In this scenario even local T cell proliferation in the inflamed nervous system occurs. These results support the paradigm of antigen presentation in the nervous system.