Expression of OX40 ligand in microglia activated by IFN-gamma sustains a protective CD4+ T-cell response in vitro.
T-cell-dependent immunity in the central nervous system (CNS) is beneficial for neuroprotection, neurogenesis and even behavior. As a highly specialized site, the CNS is speculated to possess the means to maintain T-cell immune responses through its own resident cells. Therefore, we investigated whether microglia, the most potent antigen-presenting cells residing in the CNS, could sustain T-cell responses in vitro. We showed that interferon-gamma (IFN-gamma)-activated microglia (MG(IFN-gamma)) inducibly expressed an important immune co-stimulatory molecule, OX40 ligand (OX40L). Co-culture of activated CD4(+) T cells with MG(IFN-gamma) significantly increased T-cell proliferation and decreased apoptosis, and these effects were markedly inhibited by addition of a neutralizing anti-OX40L monoclonal antibody. In addition, ligation of OX40L in MG(IFN-gamma) enhanced their production of insulin-like growth factor I (IGF-I). These results suggest that the expression of OX40L in microglia provides a molecular basis for the maintenance of T-cell survival, expansion of T cells and increased secretion of remedial growth factor from MG(IFN-gamma), which may contribute to the protective effect in the CNS.
Wang
Yanyan
Y
Department of Medical Genetics, The Third Military Medical University, Gao Tan Yan Street, Sha Ping Ba District, Chongqing 400038, PR China.
Li
Maoquan
M
Song
Min
M
Xu
Xueqing
X
Xiong
Jiaxiang
J
Yang
Xiaoya
X
Tan
Jun
J
Bai
Yun
Y
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D048708:Cell Growth Processes / Q000276:immunology; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D053278:OX40 Ligand; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D048069:Tumor Necrosis Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D012333:RNA, Messenger; D011994:Recombinant Proteins; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma