EFFECT OF HIV VERTICAL TRANSMISSION ON THE ONTOGENY OF T-CELL ANTIGENS INVOLVED IN THE REGULATION OF HUMORAL IMMUNE-RESPONSE

HIV infection causes progressive impairment of humoral immunity, inclu ding defective specific antibody production. To evaluate whether verti cal HIV infection interferes with the expression on CD4(+) lymphocytes of developmentally regulated molecules, that play a crucial role in t he generation of immunological memory (CD45 isoforms) and in attainmen t of antibody responses (CD40L), 22 HIV-infected children and 36 seror everted children born to HIV+ mothers were studied. The percentage of CD40L(+) PBMC after activation in vitro with phorbol myristate acetate (PMA) plus ionomycin was lower in HIV-infected children than in contr ols (P < 0.004). This correlated with the depletion of CD4(+) lymphocy tes (r = 0.75; P < 0.001). CD40L expression rose progressively with ag e (r = 0.36; P = 0.03) in seroreverted children, but not in HIV-infect ed children, suggesting that while in normal children in vivo antigen stimulation results in progressive attainment of CD40L expression (and thus to effective T-B cell cooperation), this process is largely defe ctive in HIV-infected children, contributing to the genesis of humoral immune deficiency. The proportion of CD4(+) cells bearing the CD45RO isoform was increased among HIV-infected infants during the first year s of life. However, the percentage of CD4(+) CD45RO(+) peripheral bloo d mononuclear cells (PBMC) progressively increased with age in control s (r = 0.69; P = 0.03), but not in HIV-infected children, showing that while vertical transmission of HIV does not prevent CD45RO expression early in life, it is associated with a disturbance of the physiologic al process of antigen priming, contributing to poor immunological memo ry to T cell-dependent antigens.