PHENOTYPE AND FUNCTION OF HEMATOPOIETIC-DERIVED CELLS IN THE CNS OF SCID MOUSE-LEWIS RAT BONE-MARROW CHIMERAS

Severe combined immunodeficient (SCID) mice previously transplanted wi th Lewis rat hematopoietic cells (SCID mouse-Lewis rat chimeras) devel oped experimental autoimmune encephalomyelitis (EAE) following injecti on with myelin basic protein (BP)-specific Lewis rat T lymphocytes. Ra t T cells did not cause EAE in non-chimeric SCID mice, Thus, in additi on to BP-specific rat T cells, transplanted rat hematopoietic cells we re involved in the development of EAE in SCID mice. In order to examin e the role of hematopoietic rat cells in the development of EAE, chime ras were constructed in SCID mice by transplanting 40 x 10(6) T cell-d epleted adult Lewis rat bone marrow cells, Single cell suspensions of brain, blood and spleen from chimeric mice were phenotyped by monoclon al antibody staining specific for mouse or rat cellular differentiatio n markers at 2 week intervals, Brain cells from chimeric mice were als o evaluated for the presence of rat antigen-presenting cells (APC). Fo ur and six weeks after hematopoietic cell transfer, mouse brain contai ned rat cells expressing the phenotypic markers (CD45+, CD11b/c+) of C NS antigen-presenting cells (APC), Six weeks after hematopoietic cell transfer, rat cells populating the CNS of chimeras were shown to funct ion as APC, stimulating BP-specific Lewis rat T lymphocytes in vitro. (C) 1996 Wiley-Liss, Inc.