ABSTRACT
Polyspecific immunoglobulins (IVIg) have been shown to reduce disease activity in multiple sclerosis (MS). To investigate the mechanisms of action of IVIg, we studied the impact of IVIg on growth and death (apoptosis) of human (auto)antigen-specific T cells. We observed a substantial suppression of proliferation of specifically activated T cells, in absence of caspase activation or DNA fragmentation. Further, neither susceptibility of T cells to undergo CD95-mediated apoptosis nor expression of apoptosis-blocking bcl-2 was modulated by IVIg. We conclude that IVIg may inhibit the reactivity of antigen-specific T cells in MS through suppression of proliferation rather than modulation of apoptosis.
Subject(s)
Apoptosis/immunology , Autoantigens/immunology , Immunoglobulins, Intravenous/immunology , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Cell Division/immunology , Cell Line , Epitopes , Humans , Immunoglobulins, Intravenous/pharmacology , In Vitro Techniques , Multiple Sclerosis/immunology , fas Receptor/immunologyABSTRACT
The efficacy of glucocorticoids in the treatment of multiple sclerosis may involve the induction of T cell apoptosis. Here, we report that glucocorticoids have two different effects on the vulnerability of human antigen-specific T cells: (i) steroids induce T cell apoptosis in a CD95-independent, but caspase-dependent manner; (ii) steroids protect T cells from CD95-mediated apoptosis which, however, is also caspase-dependent. An increase in BCL-2 expression is observed upon incubation with steroids. Thus, inhibition of CD95-mediated T cell apoptosis may be an undesirable side-effect resulting in survival of activated T cells and the maintenance of pathogenic immune responses might explain the lack of long-term glucocorticoid therapy.
