T cell helper and cytotoxic activity in Pediatric AIDS. The functional activity of T cells in children with perinatal HIV infection and the ability of the fetal or neonatal immune system to respond to HIV antigens is not well understood. Because progression to AIDS is associated with depletion of CD4+ T helper (TH) cells, the resulting changes in proportion of TH cells may affect HIV-specific cytotoxic T cell (CTL) responses and viral load, and play a critical role in determining whether infected children become long-term asymptomatic survivors or suffer from rapidly progressive disease. Secondly, if in utero immunization of HIV-specific TH cell responses occurs, this raises a possibility that in utero priming to HIV antigens may be protective against mother-infant HIV transmission. In these studies, we will determine whether changes in the TH cell population precede reduction in HIV-specific CTL responses by analyzing proportions of T cell clones with TH1, TH0 or TH2 cytokine phenotype obtained from PBMC of 30 HIV-infected children after stimulation with anti-CD3 mAb and HIV-specific peptides. The infected children, between 1 and 24 mo of age will be classified retrospectively as having slowly or rapidly progressive disease, and each child will be studied 2 times at 1-2 mo intervals and every 6 mo for 2 yr to identify patterns which may be indicative of early determination of the rate of disease progression. Cross-sectional studies will be performed on 15 children with advanced and 15 children with mild disease who are >2 yr of age to identify patterns associated with the stage of disease. The TH function will be correlated with viral load, rate of CD4+ T cell depletion, and CTL activity against HIV-env, gag, pol, and nef antigens. To determine the protective effect of HIV-specific immunity in newborns, we will analyze a profile of TH cell responses in cord blood lymphocytes from 100 infants born to HIV-infected mothers after stimulation with anti-CD3 mAb and HIV-specific peptides. Uninfected infants with TH immunity and infected infants will be followed up at 2, 4 mo and every 6 mo to 2 yr of age. Every 4th uninfected infant without HIV immunity will be included in the studies to separate effects associated with a child's own infection from factors related to maternal HIV- infection. Results of these studies may provide a means for identifying infants who are at risk for HIV infection.
| Wasik, T J; Bratosiewicz, J; Wierzbicki, A et al. (1999) Protective role of beta-chemokines associated with HIV-specific Th responses against perinatal HIV transmission. J Immunol 162:4355-64 |
| Kmieciak, D; Bednarek, I; Takiguchi, M et al. (1998) The effect of epitope variation on the profile of cytotoxic T lymphocyte responses to the HIV envelope glycoprotein. Int Immunol 10:1789-99 |
| Wasik, T J; Jagodzinski, P P; Hyjek, E M et al. (1997) Diminished HIV-specific CTL activity is associated with lower type 1 and enhanced type 2 responses to HIV-specific peptides during perinatal HIV infection. J Immunol 158:6029-36 |
