T lymphocytes promote the development of bone marrow-derived APC in the central nervous system

Certain cells within the CNS, microglial cells and perivascular macrophages , develop from hemopoietic myelomonocytic lineage progenitors in the bone m arrow (BM), Such BM-derived cells function as CNS APC during the developmen t of T cell-mediated paralytic inflammation in diseases such as experimenta l autoimmune encephalomyelitis and multiple sclerosis, We used a novel, int erspecies, rat-into-mouse T cell and/or BM cell-transfer method to examine the development and function of BM-derived APC in the CNS, Activated rat T cells, specific for either myelin or nonmyelin Ag, entered the SCID mouse C NS within 3-5 days of cell transfer and caused an accelerated recruitment o f BM-derived APC into the CNS. Rat APC in the mouse CNS developed from tran sferred rat BM within an 8-day period and were entirely sufficient for indu ction of CNS inflammation and paralysis mediated by myelin-specific rat T c ells. The results demonstrate that T cells modulate the development of BM-d erived CNS APC in an Ag-independent fashion. This previously unrecognized r egulatory pathway, governing the presence of functional APC in the CNS, may be relevant to pathogenesis in experimental autoimmune encephalomyelitis, multiple sclerosis, and/or other CNS diseases involving myelomonocytic line age cells.