Terminally differentiated CD8 cells in HIV-infected children: HIV-GAG/POL specificity and IFN-γ production

Abstract

Background: CD8 cells are key to antiviral immunity and can be divided by phenotype into early (CD28+ CD27+), intermediate (CD28-CD27+) and terminally differentiated subsets (CD28- CD27-). Despite effective HAART there is an unexplained expansion of CD8+CD28-CD27-T cells in HIV-infected children. The cytokine production and specificity of this terminally differentiated CD8 T cell subset in chronic virus infection is unclear. PATIENTS, METHODS & RESULTS: In a cohort of 26 HIV-infected children the cytokine production of terminally differentiated CD8 cells was analyzed by intracellular staining and FACS analysis and was compared to children with chronic hepatitis B infection and to healthy children. The specificity of CD8 subsets was analyzed by staining with Gag/Pol tetramers in a cohort of 13 patients. We show that an increased production of interferon-γ in terminally and early/intermediate differentiated CD8 cell subsets after stimulation is specific for HIV-infection. The expanded population of terminally differentiated CD8+CD28-CD27- T cells does include HIV Gag/Pol specific T cells in adults but not in children.

Conclusion: The expansion of terminally differentiated CD8 cells might be important for immunomodulation but in children it does not appear to play a role in HIV Gag and Pol specific immunity.