Reduced Thymic Size but No Evidence of Impaired Thymic Function in Uninfected Children Born to Human Immunodeficiency Virus-infected Mothers

Background: HIV-exposed, uninfected (HIV-EU) infants present hematologic and immunologic abnormalities at birth, and it remains to be clarified whether these abnormalities persist beyond infancy, for instance, affecting vaccination responses. Methods: Thymic size and thymic output were evaluated in 20 HIV-EU children at 15 months of age and compared with 10 age-and gender-matched controls. Regulatory T-cells (Tregs) and immune activation as well as cytokine profiles were determined, and the antibody response to Haemophilus influenzae Type b (Hib) vaccination was evaluated. Results: Thymic size was significantly lower in HIV-EU children (P = 0.011). However, CD4 and CD8 counts did not differ between HIV-EU and control children. Likewise, thymic output estimated as CD4(+) cells expressing naive (CD45RA + CD62L + CD27 +, P = 0.31) or recent thymic naive (CD45RA + CD27 + CD31 +, P = 0.13) phenotype, or CD4(+) cells containing T-cell receptor excision circles (P = 0.47) were comparable. HIV-EU children and controls had similar levels of activated cells (CD4 + CD38 + HLA-DR +, P = 0.87; CD8 + CD38 + HLA-DR +, P = 0.22), Tregs (CD4 + CD25 + CD127(low)FOXP3 +, P = 0.53), and naive Tregs (CD4 + CD25 + CD127(low)FOXP3 + CD45RA + CD27 +, P = 0.65). Finally, comparable titers of Haemophilus influenzae Type b antibodies in the 2 groups were found (P = 0.43). Conclusion: The study demonstrates reduced thymic size in HIV-EU children compared with children born to HIV-negative mothers, but no evidence of impaired thymic function, immune regulation, or antibody vaccination response was detected, suggesting that no qualitative immune deficits persist in HIV-EU children at 15 months of age.