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CD47 Expression on T Cell Is a Self-Control Negative Regulator of Type 1 Immune Response¹

Immunoregulation, Centre Hospitalier de l’Université de Montréal, Research Center, Hospital Notre-Dame, Montréal, Quebec, Canada

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-:IL-4 cytokine ratio. Although selective CD47 deficiency on DCs led to increased IL-12p70 production, CD47^–/–Tg T cells produced more IFN- 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.

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¹ This work was supported by the Canadian Institutes for Health Research (Grant MOP-53152). S.B. and V.Q.V. are recipients of the Canadian Institutes Health Research/Canada Graduate Scholarships Doctoral Award.

² Address correspondence and reprint requests to Dr. Marika Sarfati, Immunoregulation Laboratory, Centre Hospitalier de l’Université de Montréal, Hôpital Notre-Dame (Pavillon Mailloux, M4211K), 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada. E-mail address: m.sarfati{at}umontreal.ca

³ Abbreviations used in this paper: TSP, thrombospondin; Tg, transgenic; LN, lymph node; BMDC, bone marrow-derived dendritic cell; DNFB, 2,4-dinitrofluorobenzene; CHS, contact hypersensitivity response; DC, dendritic cell; SIRP, signal-regulatory protein.