Natural killer cell receptor expression reflects the role of human cytomegalovirus in the pathogenesis of a subset of CD4+ T-cell large granular lymphocytosis

A high frequency of CD4(+) T-cell large granular lymphocyte (T-LGL) lymphocytosis occurs in human leukocyte antigen (HLA) -DRB1*0701 individuals displaying monoclonal expansions of Vβ13.1+ CD4(+) T-cell clones, which specifically respond to human cytomegalovirus (HCMV) antigens. We previously reported the expression of natural killer (NK)-cell associated receptors (NKR) by HCMV-specific cytolytic CD4(+) T cells from healthy donors. In the present study a high expression of different NKR (i.e., NKG2D, killer Ig-like receptors (KIR), CD94, ILT2) was observed in CD4(+) T cells from both Vβ13.1- and Vβ13.1+ CD4(+) T-LGL cases. Remarkably, elevated numbers of CD94/NKG2C+ NK cells, previously shown to expand in association to HCMV infection, were preferentially found in Vβ13.1+ T-LGL, further supporting its role in the pathogenesis of a subset of CD4(+) T-LGL.