Differential regulation of killer cell Ig-like receptors and CD94 lectin-like dimers on NK and T lymphocytes from HIV-1-infected individuals

Abstract

NK and T lymphocytes share various cell surface receptors, including NK receptors for MHC class I molecules (NKR). NKR include killer cell Ig-like receptors (KIR) and lectin-like dimers which are composed of the invariant CD94 associated with a variety of NKG2 molecules. The combination of KIR and CD94/NKG2 dimers expressed on NK and T cell subsets defines a repertoire of MHC class I recognition. Engagement of NKR by cognate MHC class I molecules governs T and NK cell activation. We investigated the NKR distribution on NK and T cell subsets from uninfected and HIV-infected individuals, according to the clinical status, the absolute numbers of CD4 + T cells as well as the plasmatic viral load of the patients. We show that the KIR distribution on NK cells is not affected by HIV-1 infection, whereas the absolute numbers of T cells expressing specific KIR members (CD158b, p70) transiently increase in early stages of HIV infection. By contrast, the percentages of NK and T cells which express CD94 dimers increase in parallel with the disease. These results document a differential regulation of KIR and CD94 lectin-like dimers during the course of a chronic viral infection in humans and further suggest that both types of NKR are independently regulated.

Regulation of Inhibitory and Activating Killer-Cell Ig-Like Receptor Expression Occurs in T Cells After Termination of TCR Rearrangements

“…By contrast, all attempts to induce KIR in vitro on mature T or NK cells have failed so far. These results, which confirm that expression of KIRs and NKR homologous to C-type lectin is regulated through distinct pathways (43), have left open the issues as to when and how KIR are induced. The absence of both KIR transcripts (data not shown) and proteins (44) in thymocytes, and by contrast their selective expression on fully differentiated NK cells (45) and Ag-experienced T cells (26), suggests late KIR induction during lymphoid cell development.…”

“…However, whether the same factors will be required to induce KIR on precursor and mature lym- KIR expression on T cells has been mainly described on CD8 ϩ memory T cells (26). KIR engagement by autologous MHC class I molecules can regulate in vitro CD3/TCR-mediated cytotoxicity and cytokine production suggesting a role of KIR in the control of T cell activation (22,23,25,27,43,(47)(48)(49). In a previous study, activation of KIR ϩ CTL clones following recognition of tumor Ags was shown to be abrogated by KIR (50).…”

Detection of KIR3DS1 on the Cell Surface of Peripheral Blood NK Cells Facilitates Identification of a Novel Null Allele and Assessment of KIR3DS1 Expression during HIV-1 Infection

“…Similarly, murine NK1.1 ϩ CD3 ϩ T cells express inhibitory Ly49 molecules but not their activating counterparts. The definitive detection of KIR3DS1 on resting CD56 ϩ T cells is intriguing given that, except for KIR2DS4 (43), evaluation of activating KIR cell surface expression has been prevented by Ab cross-reactivity between inhibitory and activating KIR isoforms. Indeed, expression of activating KIR2DS1 and KIR2DS2 on T cells has only been shown indirectly by using flow cytometry with Abs known to react with both activators and inhibitors in conjunction with either RT-PCR to demonstrate the presence of mRNA for an activating KIR, or redirected killing assays to show an increase in cytolytic activity.…”

Ligand-Independent Exhaustion of Killer Immunoglobulin-Like Receptor-Positive CD8 + T Cells in Human Immunodeficiency Virus Type 1 Infection

“…These receptors include members of the killer immunoglobulin-like receptors (KIR) that can be both inhibiting and activating (4,8,31). In humans, peripheral blood KIR ϩ CD8 ϩ T cells represent nearly 5% of T cells in a normal healthy adult and can reach up to 30% in elderly subjects (3,36); these cells become enriched in the setting of infections with influenza virus (19), lymphocytic choriomeningitis virus (28), Listeria monocytogenes (28), hepatitis C virus (8), and HIV (4,13,33).…”