Frequency and function of KIR + CD8 + T cells in HTLV-1 infection

An efficient antiviral cytotoxic T lymphocyte (CTL) response to HTLV-1 infection maintains a low proviral load (PVL), reducing the risk of HAM/TSP. Host genotype, particularly of HLA class I, is a major determinant of CTL efficiency, and the influence of specific HLA class I alleles on HTLV-1 immunity is well documented. We recently showed that killer immunoglobulin-like receptor (KIR) genotype also influences CTL efficiency, by affecting HLA class I-mediated HTLV-1 immunity. Possession of the KIR2DL2 gene enhanced the effect of known protective or detrimental HLA class I alleles on PVL and HAM/TSP risk. This study aims to profile the frequency and function of CD8+ T cells expressing KIR2DL2 and other KIRs in HTLV-1 infection. Analysing total KIR expression showed the presence of KIR+CD8+ T cells, NK cells and CD4+ T cells in PBMCs from uninfected and HTLV-1+ donors. A subset of HTLV-1+ donors had high frequencies of total KIR+CD8+ T cells. Analysing individual KIRs revealed the presence of KIR2DL2+CD8+ T cells in HTLV-1+ donors. Preliminary data from PBMCs stimulated with Tax peptides indicates that KIR2DL2+CD8+ T cells constitute a very small proportion of the IFNγ-producing Tax-specific CD8+ T cell population. HTLV-1+ asymptomatic carriers had higher frequencies of IFNγ-producing Tax-specific KIR2DL2+CD8+ T cells than donors with HAM/TSP did. Further work is underway to characterise the function of Tax-specific CD8+ T cells by staining with anti-CD107a, anti-IFNγ and the HLA-A2/Tax11-19 pentamer, and to compare the frequency and function of KIR2DL2+CD8+ T cells with those expressing other 2-domain KIRs.