HIV-infected children on highly active antiretroviral therapy (HAART) with immune reconstitution have impaired humoral responses to vaccines and more rapidly waning antibody levels compared to uninfected children. However, little is known about their T cell function. Data from HIV-infected adults demonstrated diminished CD4+ effector memory T cell response to measles and VZV despite normal CD4 counts. Whether similar deficiencies of T cell immunity are present in HIV-infected children is of interest, particularly given the potential role of the thymus in maintaining function in children.
We recruited 20 perinatally HIV-infected children on HAART with viral suppression and immune reconstitution. Using flow cytometry on whole blood, we analyzed resting T cell phenotypes and effector memory T cell responses to measles, VZV and CMV. Responses were compared to healthy uninfected age-matched controls (n=7). Resting and viral-specific regulatory T cell (Treg) responses were also evaluated, as well as innate immune response.
Unlike adults, the children’s resting T cell subsets were shifted towards the naïve (CD4+CD45RO-) rather than the memory (CD4+CD45RO+) T cell pool. At rest, they did not show a more activated phenotype (CD4+CD45RO+CD69+IFNγ+) compared to controls. In terms of T cell function, HIV-infected children did not show deficiencies in antigen-specific memory effector T cell responses (CD4+CD45RO+CD69+IFNγ+) when compared to healthy controls. Differences were not observed even when stratified by severity of immunosuppression, age, or time elapsed before initiation of HAART. Although higher number of Tregs is generally associated with HIV in adults, our study showed no significant differences in the number of natural Tregs (CD4+CD45RO+CD25hiCD127lo) between perinatally-infected children and controls. APC (DCs and monocytes) were also unaffected in this population and they were able to mount comparable response to LPS stimulation (as measured by CD40 and TNF-α expression for monocytes and DC respectively).
Perinatally infected children on HAART maintain relatively normal innate and T cell adaptive immune profiles which appear to be unaffected even when their CD4 nadirs were in the severely immunocompromised category at the time of diagnosis.