Gangliosides suppress the proliferation of autoreactive cells in experimental allergic encephalomyelitis: ganglioside effects on IL-2 activity.
Gangliosides have been shown to suppress human and murine lymphocyte proliferative responses in vitro. We tested the suppressive effects of gangliosides on the proliferation of autoreactive lymphoid cells obtained from Lewis rats with experimental allergic encephalomyelitis (EAE). Exogenous rat brain gangliosides inhibited both antigen- and mitogen-induced proliferation by as much as 79 and 93%, respectively. Gangliosides similarly inhibited the antigen-induced proliferation of a myelin basic protein (MBP)-reactive T-cell line which is able to passively induce EAE. Suppression was greatest when gangliosides were added at the initiation of culture, and was not abrogated by supraoptimal antigen concentration. Interleukin 2 (IL-2) activity in culture supernatants was not diminished by the addition of gangliosides. Gangliosides did not inhibit the IL-2-induced proliferation of a murine IL-2-dependent cell line, CTLL-20, unless the IL-2 was first preincubated with gangliosides before the addition of CTLL-20. Preincubation of CTLL-20 with gangliosides resulted in no inhibition of the subsequent responses to IL-2. Exogenous gangliosides did not decrease the binding of a monoclonal antibody directed against the rat cell surface IL-2 receptor. Addition of exogenous IL-2 to ganglioside-suppressed cultures had no effect or only partially restored the proliferative responses. Therefore, gangliosides were shown to inhibit the proliferation of autoreactive lymphoid cells without affecting IL-2 production or IL-2 receptor expression.
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005732:Gangliosides / Q000494:pharmacology*; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D004676:Myelin Basic Protein / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D005732:Gangliosides; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D004676:Myelin Basic Protein; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2