DIMINISHED HIV-SPECIFIC CTL ACTIVITY IS ASSOCIATED WITH LOWER TYPE-1 AND ENHANCED TYPE-2 RESPONSES TO HIV-SPECIFIC PEPTIDES DURING PERINATAL HIV-INFECTION

The early development of symptoms and the rapid progression of disease in some vertically infected infants are thought to reflect in part th e immaturity of their immune systems, We examined the relationship bet ween HIV-specific CTL activity and the profile of cytokine production induced by mAb to CD3 and HIV envelope (env) peptides P18 and T1 in PB MC derived from 0.6- to 3.6-yr-old children with perinatal HIV infecti on. Cellular immunity against HIV was demonstrated only during early s tages of disease, whereas the responses were either undetectable or at background levels in HIV-infected children with rapidly progressing d isease and in uninfected children of HIV+ and HIV- mothers, Levels of IL-2 mRNA in anti-CD3 mAb- and env peptide-induced PBMC varied and wer e increased in the infected children with high frequencies of HIV-spec ific CTL precursors, Analysis of IFN-gamma and IL-4 production by CD4( +) T cell clones obtained from cultures stimulated with anti-CD3 mAb o r the env peptides showed an increased proportion of Th2 and Th0 clone s in HIV-infected children with lower HIV-specific CTL activity, where as children with high CTL activity had increased numbers of Th1 clones , The results of these studies suggest that decreases in CTL activity to the virus might be associated with the induction of a type 2 cytoki ne response, These findings underline the role of cytokines in the gen eration of HIV-specific CTL responses and may be important for the dev elopment of immunomodulatory and vaccine strategies to interrupt verti cal transmission of HIV.