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T lymphocytes promote the development of bone marrow-derived APC in the central nervous system
S Subramanian1, D N Bourdette, C Corless
1Veterans' Affairs Medical Center, Portland, OR, 97201, USA.
Abstract:
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.
Insights
Bone marrow-derived cells in the central nervous system (CNS) act as antigen-presenting cells (APCs). T cells accelerate the development of these APCs, influencing CNS inflammation and paralysis in diseases like multiple sclerosis.
Area of Science:
- Neuroimmunology
- Cellular Immunology
- Hematopoiesis
Background:
- Microglial cells and perivascular macrophages in the CNS originate from bone marrow (BM) myelomonocytic progenitors.
- These BM-derived cells function as antigen-presenting cells (APCs) in CNS diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS).
Purpose of the Study:
- To investigate the development and function of BM-derived APCs in the CNS using an interspecies cell transfer model.
- To elucidate the regulatory mechanisms governing APC presence in the CNS.
Main Methods:
- An interspecies, rat-into-mouse T cell and/or BM cell-transfer method was employed.
- Activated rat T cells (myelin or nonmyelin antigen-specific) were transferred into SCID mice.
- Recruitment and development of BM-derived APCs in the mouse CNS were analyzed.
Main Results:
- Activated rat T cells accelerated the recruitment of BM-derived APCs into the CNS within 3-5 days.
- Rat APCs developed from transferred rat BM within 8 days and induced CNS inflammation and paralysis.
- T cells modulated the development of BM-derived CNS APCs in an antigen-independent manner.
Conclusions:
- A novel regulatory pathway exists where T cells influence the development of BM-derived APCs in the CNS.
- This pathway is antigen-independent and may play a role in the pathogenesis of CNS diseases like EAE and MS.