T suppressor hybridomas and interleukin-2-dependent lines induced by copolymer 1 or by spinal cord homogenate down-regulate experimental allergic encephalomyelitis.
Suppressor T (Ts) hybridomas and interleukin-2-dependent T cell lines were established from spleens of mice, which had been rendered unresponsive to experimental allergic encephalomyelitis (EAE) either by mouse spinal cord homogenate or by the synthetic suppressant copolymer 1 (Cop 1). The Ts hybridoma supernatants and the Ts line cells specifically suppressed the in vitro response to the encephalitogenic myelin basic protein (BP), as indicated by inhibition of both the proliferation and interleukin-2-secretion responses of a BP-specific T cell line. Moreover, these Ts cells prevented the development of actively induced EAE in vivo. All hybridomas and lines were most effective when injected at the time of disease induction, thus suggesting that they operate as effector suppressor cells, and functionally inhibit encephalitogenic responses. The data presented here suggest that the suppressor cells are stimulated by the protective epitopes included in the BP as well as in the Cop 1 molecules and that they play an active role in the regulation of EAE. The generation of Ts lines and hybridomas, which have been induced by Cop 1, establish the specific stimulation of suppressor cells to EAE as a mechanism underlying the therapeutic activity of Cop 1.
Aharoni
R
R
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Teitelbaum
D
D
Arnon
R
R
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology*; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007376:Interleukin-2; D010455:Peptides; C021759:(T,G)-A-L