Cytolytic T lymphocytes displaying natural killer (NK)-like activity: expression of NK-related functional receptors for HLA class I molecules (p58 and CD94) and inhibitory effect on the TCR-mediated target cell lysis or lymphokine production

Abstract

Natural killer (NK) cells express surface receptors for defined groups of HLA class I alleles. The specific interaction between these receptors and HLA class I molecules expressed on target cells results in inhibition of NK-mediated target cell lysis. In this report, we analyzed whether similar mechanisms were operating in cytolytic T lymphocytes (CTLs) capable of lysing NK-sensitive target cells. T cell clones were screened for their ability to lyse K562 target cells. The selected clones expressed either gamma delta or alpha beta TCR. The majority of these clones failed to lyse the HLA class I+ R8/15375 cell line; however, upon addition of the previously described A6-136 (IgM) or 6A4 F(ab')2 anti-HLA class I mAbs, target cells were efficiently lysed. Lysis of autologous phytohemagglutinin blasts in the presence of anti-HLA class I mAbs occurred primarily with TCR gamma delta+ CTLs. Recognition of HLA class I molecules on target cells implies the expression of NK-related specific receptors in CTL clones. Indeed, phenotypic analysis of > 300 CTL clones with NK-like activity revealed that 28% expressed p58 molecules (specific for HLA-C alleles) while 30% expressed CD94 molecules (specific for the Bw6 specificity). These receptor molecules were found to function as inhibitory receptors, as revealed by the effect of anti-p58 or anti-CD94 mAbs (of IgG isotype) on the lysis of the Fc gamma R+ K562 target cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Emergence of CD8+ T Cells Expressing NK Cell Receptors in Influenza A Virus-Infected Mice

“…In the bone marrow of mice, expression of NK1.1 and Ly49 molecules have been shown to be associated with memory T cells (23). Studies performed in humans have described activated CD8 ϩ T cells that possess NKR-P1C (24) or inhibitory NK cell receptors such as p58.2 (25-27), NKB-1 (27,28), and CD94/NKG2A (25,29,30). Similar T cells have also been found in HIV-infected patients (31).…”

The Repertoire of Killer Cell Ig-Like Receptor and CD94:NKG2A Receptors in T Cells: Clones Sharing Identical αβ TCR Rearrangement Express Highly Diverse Killer Cell Ig-Like Receptor Patterns

“…Although first characterized on NK cells, the KIR and CD94: NKG2 families are also found on subpopulations of peripheral blood ␣␤ T cells (21)(22)(23), ␥␦ T cells (24,25), and T cells in the liver (26). Both CD4 and CD8 ␣␤ T cells can express NKR, although the latter are much more common (27).…”

“…Both CD4 and CD8 ␣␤ T cells can express NKR, although the latter are much more common (27). The NKR expressed by T cells have been shown to be functional; stimulatory signals coming from the TCR can be overridden by inhibitory signals generated through a KIR or CD94:NKG2A receptor, thereby inhibiting target cell cytolysis and cytokine release (22)(23)(24)(27)(28)(29)(30)(31)(32)(33). A common feature of NKR ϩ T cells is a cell surface phenotype that is characteristic of memory T cells; they lack CD28 and CD45RA, mostly express CD45RO, and have high levels of CD18, CD44, CD29, and CD57 (28,34).…”

KIR2DL5, a Novel Killer-Cell Receptor with a D0-D2 Configuration of Ig-Like Domains

“…K iller-cell Ig-like receptors (KIR), 5 also known as killercell inhibitory receptors, are glycoproteins of the Ig superfamily expressed on the surfaces of human NK cells and a subset of T lymphocytes (1)(2)(3)(4)(5). They comprise 12 protein groups, possibly encoded by different genes (1-3, 6 -10).…”