Differential induction of CD94 and NKG2 in CD4 helper T cells. A consequence of influenza virus infection and interferon‐γ?

Abstract

Influenza A virus causes worldwide epidemics and pandemics and the investigation of memory T helper (Th) cells that help maintain serological memory following infection is important for vaccine design. In this study we investigated CD94 and NKG2 gene expression in memory CD4 T-cell clones established from the spleens of C57BL/10 (H-2(b)) and BALB/c (H-2(d)) mice infected with influenza A virus (H3N2). CD94 and NKG2A/C/E proteins form heterodimeric membrane receptors that are involved in virus recognition. CD94 and NKG2 expression have been well characterized in natural killer (NK) and cytotoxic T cells. Despite CD94 being potentially an important marker for Th1 cells involved in virus infection, however, there has been little investigation of its expression or function in the CD4 T-cell lineage and no studies have looked at in-vivo-generated Th cells or memory cells. We show in this study that in-vivo-generated CD4 Th1 cells, but not Th2 cells, exhibited full-length CD94 and NKG2A gene expression following activation with viral peptide. For NKG2A, a novel 'short' (possibly redundant) truncated isoform was detectable in a Th2 cell clone. Another member of the NK receptor family, NKG2D, but not NKG2C or E, was also differentially expressed in Th1 cells. We show here that CD94 and NKG2A may exist as multiple isoforms with the potential to distinguish helper T-cell subsets.

HBHA-Induced Polycytotoxic CD4+ T Lymphocytes Are Associated with the Control of Mycobacterium tuberculosis Infection in Humans

“…As specific surface markers for CD4 + CTL have not yet been identified, their sorting for functional studies is currently impossible. Apart from CD107a and CD107b, NK group 2 (NKG2A) (27,28) and NKG2D (28,29) have been proposed. We investigated whether NKG2A or NKG2C could identify HBHAinduced CD4 + PCTL, but only a very small proportion of them stained positive for either surface marker, even though all NKG2A + or NKG2C + CD4 + blasts could be found within the HBHA-induced CD4 + PCTL subpopulation (data not shown).…”

Expansions of NK-like αβT cells with chronologic aging: Novel lymphocyte effectors that compensate for functional deficits of conventional NK cells and T cells

“…TCR engagement alone has been shown to induce expression for some NKRs on T cells in vitro (Huard & Karlsson, 2000). Several studies suggest the importance of the cytokine milieu, with certain NKRs being preferentially expressed in response to specific cytokines or combinations thereof in a variety of biological situations (Ponte et al , 1998; Roberts et al , 2001; Burgess et al , 2006; von Geldern et al , 2006; Graham et al , 2007; Crane et al , 2010). However, limiting dilution analysis of in vitro generated T cell clones show that even clonotypes growing within the same environment express different NKRs (Snyder et al , 2002).…”

Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells

“…45,46 However, in contrast to induction of cytotoxicity via IL-12, mainly IL-2 has been implicated in this process. 43 Thus, Eomes-dependent cytotoxicity can be induced in both innate and adaptive lymphocyte populations, and type 1-inducing proinflammatory conditions favor its development.…”