CD47 expression on T cell is a self-control negative regulator of type 1 immune response.
The cytokine milieu and dendritic cells (DCs) direct Th1 development. Yet, the control of Th1 polarization by T cell surface molecules remains ill-defined. We here report that CD47 expression on T cells serves as a self-control mechanism to negatively regulate type 1 cellular and humoral immune responses in vivo. Th2-prone BALB/c mice that lack CD47 (CD47(-/-)) displayed a Th1-biased Ab profile at steady state and after immunization with soluble Ag. CD47(-/-) mice mounted a T cell-mediated exacerbated and sustained contact hypersensitivity (CHS) response. After their adoptive transfer to naive CD47-deficient hosts 1 day before immunization with soluble Ag, CD47(-/-) as compared with CD47(+/+)CD4(+) transgenic (Tg) T cells promoted the deviation of Ag-specific T cell responses toward Th1 that were characterized by a high IFN-gamma:IL-4 cytokine ratio. Although selective CD47 deficiency on DCs led to increased IL-12p70 production, CD47(-/-)Tg T cells produced more IFN-gamma and displayed higher T-bet expression than CD47(+/+) Tg T cells in response to OVA-loaded CD47(-/-) DCs. CD47 as part of the host environment has no major contribution to the Th1 polarization responses. We thus identify the CD47 molecule as a T cell-negative regulator of type 1 responses that may limit unwanted collateral damage to maximize protection and minimize host injury.
Immunoregulation, Centre Hospitalier de l'Université de Montréal, Research Center, Hospital Notre-Dame, Montréal, Quebec, Canada.
Salim
S
Bouguermouh
Vu Quang
VQ
Van
Julie
J
Martel
Patrick
P
Gautier
Manuel
M
Rubio
Marika
M
Sarfati
D000818:Animals; D051928:CD47 Antigen / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D018836:Inflammation Mediators