Function and phenotype of immature CD4⁺ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers

The function and phenotypes of CD4⁺ lymphocytes in infants are different than in adults and are modulated by maturational changes and exposure to environmental antigens. Infants of non-human immunodeficiency virus (HIV)-infected mothers and uninfected infants of HIV-infected mothers, 0 to 6 months of age, were examined for CD4⁺ lymphocyte function by in vitro interleukin-2 (IL-2) production and for CD4⁺ phenotypes by three-color flow cytometry. A minority of these uninfected infants (28%) had functional responses similar to those of healthy adult women (IL-2 production in response to anti-CD3, alloantigen, and mitogen), while the remainder were capable of responding to alloantigen and mitogen but not to anti-CD3. We did demonstrate reduced phytohemagglutinin-stimulated IL-2 production in uninfected infants born to HIV-seropositive mothers compared to that in infants from seronegative mothers. The proportions of CD3⁺ CD4⁺, CD4⁺ HLA- DR^-CD38⁺, and CD4⁺ CD45RA⁺ RO^- (naive) lymphocytes were much higher in infants than in adults, and the proportions of CD4⁺ CD45RA RO⁺ (memory) and CD4⁺ CD25⁺ (IL-2 receptor-bearing) lymphocytes were lower in infants than in adults. The proportions of activated (CD4⁺ HLA-DR⁺ CD38⁺) and memory (CD4⁺ CD45RA^- RO⁺) lymphocytes were increased in uninfected infants of HIV-infected mothers compared to infants of uninfected mothers. Therefore, T- helper-cell function is immature in many infants, but the CD4⁺ lymphocytes of some HIV-exposed, uninfected infants have been stimulated by antigen at an early age.