INDUCTION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN SEVERE COMBINED IMMUNODEFICIENT MICE RECONSTITUTED WITH ALLOGENEIC OR XENOGENEIC HEMATOPOIETIC-CELLS

Severe combined immunodeficient (SCID) C.B-17-scid/scid (H-2d) strain mice are deficient for T and B lymphocytes and lack all of the immune functions associated with these cell types. Experimental autoimmune en cephalomyelitis (EAE) was induced in chimeric SCID mice that had been previously reconstituted with allogeneic mouse or xenogeneic rat hemat opoietic stem cells from EAE-susceptible donor strains. Encephalitogen ic, myelin Ag-specific, T lymphocytes selected from SJL mice, Lewis ra ts, or Buffalo rats transferred passive EAE into chimeric SCID mice re constituted with SJL mouse, Lewis rat, or Buffalo rat hematopoietic ce lls, respectively. SCID mice reconstituted with Lewis rat hematopoieti c tissue and thymus were also susceptible to EAE induced by active imm unization with the myelin proteolipid protein synthetic peptide PLP Sl 39-151. T lymphocytes recovered from the spleens of SCID mouse-rat ch imeras with EAE proliferated upon in vitro stimulation with myelin Ag presented by APC syngeneic to the transplant donor, and rat T lymphocy tes selected in vitro from SCID mouse-rat chimeras with EAE transferre d EAE back into naive recipient rats. Thus, the immunodeficiency prese nt in SCID mice can be overcome at least partially by hematopoietic ti ssue transplantation from allogeneic or xenogeneic donors. Furthermore , allogeneic SJL mouse and xenogeneic Lewis or Buffalo rat myelin Ag-s pecific T cells can transfer EAE between strains and species, respecti vely, into recipient SCID mouse chimeras.