A subset of functional effector‐memory CD8+ T lymphocytes in human immunodeficiency virus‐infected patients

Abstract

CD8⁺ T cells provide protective immune responses via both cytolytic and non-cytolytic mechanisms in subjects infected with human immunodeficiency virus (HIV). In the present study, we investigated the CD28 expression of CD8⁺ T cells present in the peripheral blood lymphocyte subset isolated from chronically HIV-infected subjects. Using flow cytometric analysis, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28-negative, intermediate (int) and high, was seen for CD8⁺ T cells. Our study focused mostly on the CD28^int CD8⁺ T cells. The CD28^int CD8⁺ T cells are CD57^– CD27⁺ CD45RO⁺ CD45RA^– CCR7^low CD62L^int. The proliferative capacity of CD28^int CD8⁺ T cells was intermediate between those of CD28^– CD8⁺ T cells and CD28^high CD8⁺ T cells. The CD28^int CD8⁺ T cells are specific for HIV, cytomegalovirus (CMV) and Epstein–Barr virus (EBV) antigens as measured by human leucocyte antigen pentamer binding and produce both intracellular interferon-γ and tumour necrosis factor-α in response to their cognate viral peptides. The CD28^int CD8⁺ T cells have HIV-specific, CMV-specific and EBV-specific cytotoxic activity in response to their cognate viral peptides. These findings indicate that a subset of functional effector-memory CD8⁺ T cells specific for HIV, CMV and EBV antigens may contribute to an efficient immune response in HIV-infected subjects.