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)-[gamma] 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 14 h with CMV antigens, the superantigen Staphylococcus aureus enterotoxin B or medium, and labeled for identification of central memory (TCM) and effector memory (TEM) CD4+ T cells, and for the intracellular detection of induced CD154, IFN-[gamma] and/or IL-2 by flow cytometry.
Results: Compared with CD38- cells, CD38+ TCM cells from patients had less CD40L induction after CMV stimulation, and increased IFN-[gamma] response. Patients' CD38+ TEM cells showed a lower IL-2 response, and tended to have a greater IFN-[gamma] response, in which CD154 induction frequently failed. CMV-specific responses of patients' CD38+ TCM and TEM cells were dominated by IFN-[gamma], and almost all IL-2+ cells co-expressed IFN-[gamma]. IL-2 responses to the polyclonal activator S. aureus enterotoxin B were also significantly less frequent among CD38+ TCM and TEM cells than in CD38- cells.
Conclusion: Patients' CD38+ memory CD4+ T-cell responses to CMV favor the effector cytokine IFN-[gamma] over IL-2, in the context of deficient CD154 induction, which may limit co-stimulation, proliferation and survival.
(C) 2014 Lippincott Williams & Wilkins, Inc.