Cytomegalovirus-specific responses of CD38 R memory T cells are skewed towards IFN-γ and dissociated from CD154 in HIV-1 infection

Objective:Despite the strong correlation of T-cell CD38 expression with HIV disease progression, evidence linking CD38 expression and dysfunction at the single cell level is scant. Since CD38(+) memory CD4(+) T cells, especially those from HIV-infected persons, fail to induce CD154 (CD40L) while responding to a superantigen with interferon (IFN)- or interleukin (IL)-2, we aimed to determine if recall responses to cytomegalovirus (CMV) were similarly affected in the CD38(+) memory CD4(+) T-cell subpopulation.Design and methods:Peripheral blood mononuclear cells from HIV+ patients and healthy controls were incubated 14h with CMV antigens, the superantigen Staphylococcus aureus enterotoxin B or medium, and labeled for identification of central memory (T-CM) and effector memory (T-EM) CD4(+) T cells, and for the intracellular detection of induced CD154, IFN- and/or IL-2 by flow cytometry.Results:Compared with CD38(-) cells, CD38(+) T-CM cells from patients had less CD40L induction after CMV stimulation, and increased IFN- response. Patients' CD38(+) T-EM cells showed a lower IL-2 response, and tended to have a greater IFN- response, in which CD154 induction frequently failed. CMV-specific responses of patients' CD38(+) T-CM and T-EM cells were dominated by IFN-, and almost all IL-2(+) cells co-expressed IFN-. IL-2 responses to the polyclonal activator S. aureus enterotoxin B were also significantly less frequent among CD38(+) T-CM and T-EM cells than in CD38(-) cells.Conclusion:Patients' CD38(+) memory CD4(+) T-cell responses to CMV favor the effector cytokine IFN- over IL-2, in the context of deficient CD154 induction, which may limit co-stimulation, proliferation and survival. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins