CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation.
Our laboratory discovered that CD4-positive (CD4+) T cells of the immune system convey transitory neuroprotection to injured mouse facial motoneurons (FMNs) (Serpe et al., 1999, 2000, 2003). A fundamental question in the mechanisms responsible for neuroprotection concerns the identity of the cell(s) that serves as the antigen-presenting cell (APC) to activate the CD4+ T cells. Here, we first establish that CD4+ T cells reactive to non-CNS antigen fail to support FMN survival and, second, demonstrate a two-compartment model of CD4+ T cell activation. Mouse bone marrow (BM) chimeras were developed that discriminate between resident antigen-presenting host cell and BM-derived antigen-presenting donor cell expression of major histocompatibility complex II within central and peripheral compartments, respectively. After facial nerve transection, neither compartment alone is sufficient to result in activated CD4+ T cell-mediated FMN survival. Rather, CD4+ T cell-mediated neuroprotection appears to depend on both resident microglial cells in the central compartment and a BM-derived APC in the peripheral compartment. This is the first in vivo report demonstrating a neuroprotective mechanism requiring APC functions by resident (i.e., parenchymal) microglial cells.
Byram
Susanna C
SC
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Maywood, Illinois 60153, USA.
Carson
Monica J
MJ
DeBoy
Cynthia A
CA
Serpe
Craig J
CJ
Sanders
Virginia M
VM
Jones
Kathryn J
KJ
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D019771:Axotomy; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002451:Cell Compartmentation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D019610:Cytoprotection / Q000235:genetics / Q000276:immunology*; D005154:Facial Nerve / Q000166:cytology / Q000502:physiology; D005260:Female; D005802:Genes, MHC Class II; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011828:Radiation Chimera
D000941:Antigens