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 marrow (BM). Such BM-derived cells function as CNS APC during the development of T cell-mediated paralytic inflammation in diseases such as experimental autoimmune encephalomyelitis and multiple sclerosis. We used a novel, interspecies, 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 CNS within 3-5 days of cell transfer and caused an accelerated recruitment of BM-derived APC into the CNS. Rat APC in the mouse CNS developed from transferred rat BM within an 8-day period and were entirely sufficient for induction of CNS inflammation and paralysis mediated by myelin-specific rat T cells. The results demonstrate that T cells modulate the development of BM-derived CNS APC in an Ag-independent fashion. This previously unrecognized regulatory 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 lineage cells.
Subramanian
S
S
Veterans' Affairs Medical Center, Portland, OR, 97201, USA.
Bourdette
D N
DN
Corless
C
C
Vandenbark
A A
AA
Offner
H
H
Jones
R E
RE
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000637:transplantation; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D016026:Bone Marrow Transplantation; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D016130:Immunophenotyping; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014183:Transplantation, Heterologous