Tm1 cells, a subset of T cells with NK cell and memory CD8 T‐cell features

Abstract

Tolerance of NK cell toward self is ensured in part by inhibitory receptors for MHC class I receptors. These receptors include killer cell Ig-like receptors (KIRs) and leukocyte Ig-like receptors (LIRs) in humans, Ly49 molecules in mice, as well as CD94/NKG2A heterodimers in both species. These receptors can also be expressed on T cells. Whereas CD94/NKG2A heterodimers can be readily expressed after T-cell activation, the induction of KIR or LIR on human T cells, as well of Ly49 molecules on mouse T cells, appears more tightly regulated. We will present data that characterize T memory type 1 cells (Tm1 cells), the subset of CD8+ T cells that express KIR/LIR in humans or Ly49 in mice. Nakajima T, Goek O, Zhang X, et al. De novo expression of killer immunoglobulin-like receptors and signaling proteins regulates the cytotoxic function of CD4 T cells in acute coronary syndromes. Circ Res [Epub ahead of print]. Induction of KIR on CD4+ T cells. Such expansions occur in acute coronary syndromes as well as in rheumatoid arthritis patients. Wechsler J, Bagot M, Nikolova M, et al. Killer cell immunoglobulin-like receptor expression delineates in situ Sezary syndrome lymphocytes. J Pathol 2003: 199 (1): 77–83. Sezary cells selectively express KIR3DL2. This article reviews these very important sets of information. Romagnani C, Pietra G, Falco M, et al. Identification of HLA-E-specific alloreactive T lymphocytes: a cell subset that undergoes preferential expansion in mixed lymphocyte culture and displays a broad cytolytic activity against allogeneic cells. Proc Natl Acad Sci USA 2002: 99 (17): 11328–11333. First complete description of HLA-E-restricted T cells is KIR+ T cells. Ugolini S, Arpin C, Anfossi N, et al. Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T cells. Nat Immunol 2001: 2 (5): 430–435. First demonstration that KIR engagement can participate in the survival of Tm1 cells. Vely F, Peyrat M, Couedel C, et al. Regulation of inhibitory and activating killer-cell Ig-like receptor expression occurs in T cells after termination of TCR rearrangements. J Immunol 2001: 166 (4): 2487–2494. Young N T, Uhrberg M, Phillips J H, Lanier L L, Parham P. Differential expression of leukocyte receptor complex-encoded Ig-like receptors correlates with the transition from effector to memory CTL. J Immunol 2001: 166 (6): 3933–3941. These two papers demonstrate that KIR are acquired after VDJ recombination. Andre P, Brunet C, Guia S, et al. Differential regulation of killer cell Ig-like receptors and CD94 lectin-like dimers on NK and T lymphocytes from HIV-1-infected individuals. Eur J Immunol 1999: 29 (4): 1076–1085. This paper first shows that the mechanisms involved in the regulation of CD94/NKG2A and KIR expression in vivo are different. Bakker A B, Phillips J H, Figdor C G, Lanier L L. Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, γδ T cells, and antigen-specific CTL. J Immunol 1998: 160 (11): 5239–5245. De Maria A, Ferraris A, Guastella M, et al. Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: impairment of specific cytolytic functions. Proc Natl Acad Sci USA 1997: 94 (19): 10285–10288. Together with several other publications from several groups, these two articles show that KIR engagement can inhibit T-cell effector function.