Abstract
The signaling lymphocyte activation molecule (SLAM) family receptor, 2B4/CD244, was first implicated in anti-viral immunity by the discovery that mutations of the SLAM-associated protein, SAP/SH2D1A, impaired 2B4-dependent stimulation of T and natural killer (NK) cell anti-viral functions in X-linked lymphoproliferative syndrome patients with uncontrolled Epstein–Barr virus infections. Engagement of 2B4 has been variably shown to either activate or inhibit lymphocytes which express this receptor. While SAP expression is required for stimulatory functions of 2B4 on lymphocytes, it remains unclear whether inhibitory signals derived from 2B4 can predominate even in the presence of SAP. Regardless, mounting evidence suggests that 2B4 expression by NK and CD8 T cells is altered by virus infection in mice as well as in humans, and 2B4-mediated signaling may be an important determinant of effective immune control of chronic virus infections. In this review, recent findings regarding the expression and function of 2B4 as well as SAP on T and NK cells during virus infection is discussed, with a focus on the role of 2B4–CD48 interactions in crosstalk between innate and adaptive immunity.
Highlights
Immunity to virus infection involves the complex interplay of many different leukocytes, including natural killer (NK) cells (Bukowski et al, 1983; Biron et al, 1989) and CD8 T cells (Zinkernagel and Welsh, 1976)
Expression of some NK cell receptors (NKR) is up-regulated on activated T cells and this expression is often sustained at a high level on virusspecific T cells that have lost functionality or become exhausted in the context of chronic virus infection (Vivier and Anfossi, Abbreviations: Epstein– Barr virus (EBV), Epstein–Barr virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HTLV-I, human T-lymphotropic virus I; IFN, interferon; immunoreceptor tyrosine-based switch motifs (ITSM), immunoreceptor tyrosine-based switch motif; KIR, killer immunoglobulin-like receptor; LCMV, lymphocytic choriomeningitis virus; MCMV, murine cytomegalovirus; MHC, major histocompatibility complex; NK, natural killer; NKR, NK cell receptor; NTB-A, NK-T-B-antigen; PD-1, programed death-1; SLAMassociated protein (SAP), SLAM-associated protein; SLAM, signaling lymphocyte activation molecule; TGF-β, transforming growth factor-beta; XLP, X-linked lymphoproliferative. 2004; Crawford and Wherry, 2009)
CONCLUDING REMARKS Immunity to virus infection often involves NK cells and virusspecific T cells, whose responses must be regulated in order to prevent excessive lymphoproliferation that could lead to immunopathology, autoimmunity, and cancer
Summary
Immunity to virus infection involves the complex interplay of many different leukocytes, including natural killer (NK) cells (Bukowski et al, 1983; Biron et al, 1989) and CD8 T cells (Zinkernagel and Welsh, 1976). Natural killer cell anti-viral function is further regulated by a variety of activating and inhibitory receptors that engage stressinduced proteins (Raulet, 2003) or self-specific MHC antigens (Brutkiewicz and Welsh, 1995) on virus-infected cells.
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