HIV-1 infection is characterized by loss of CD56dim CD16+ NK cells and increased terminal differentiation on various lymphocyte subsets. We identified a decrease of CD57− and CD57dim cells but not of CD57bright cells on CD56dim CD16+ NK cells in chronic HIV infection. Increasing CD57 expression was strongly associated with increasing frequencies of killer immunoglobulin-like receptors (KIRs) and granzyme B-expressing cells but decreasing percentages of cells expressing CD27+, HLA-DR+, Ki-67+, and CD107a. Our data indicate that HIV leads to a decline of less-differentiated cells and suggest that CD57 is a useful marker for terminal differentiation on NK cells.

These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells.

؉ NK cells exhibited a more functional profile, as detected by cytokine production and degranulation. IMPORTANCE We demonstrate that the frequency of highly functional CD8؉ NK cells is inversely associated with HIV-related disease markers and linked with delayed disease progression. These results thus indicate that CD8؉ NK cells represent a novel NK cell-derived, innate immune correlate with an improved clinical outcome in HIV infection.