Background:  Cell-mediated immunity and T cell maturation are altered in HIV^­ newborns of HIV⁺ mothers. We verified whether these abnormalities are maintained years after intra-utero exposure to HIV or HIV antigens had ceased by studying sero-reverter, healthy adolescents born of HIV⁺ mothers. Endogenous antivirals (APOBEC and TRIM proteins) were also assessed in all the adolescents.

Methods:  Immunological analyses were performed in 16 sero-reverter healthy adolescents (age range 11.3 to 19.9 years) born of HIV⁺ mothers. Results were compared to those obtained in 20 healthy adolescents born of HIV^­ mothers (age range 12.3 to 19.3 years) and in 16 HIV⁺ adolescents born to HIV⁺ mothers (age range 12.2 to 19.6 years ). None of the sero-reverters or HIV⁺ was exposed in utero, at delivery, or neonatally to antiviral drugs. Hepatitis C virus (HCV) co-infection was present in 8 sero-reverter and 7 HIV⁺ adolescents. CD4 counts and percentages were comparable at birth in sero-reverters and HIV⁺, but were significantly reduced in HIV by month 12 after birth. Weight at birth and gestational age were comparable among the 3 groups examined. At the time of the study height, weight, and body mass index were comparable between sero-reverters and healthy adolescents; these parameters were reduced, albeit not significantly, in HIV⁺ individuals.

Results:  In sero-reverters, B lymphocytes were augmented and natural killer (NK) cells were reduced compared with healthy controls, and additionally in seroreverter CD4 EM (CCR7^­/45RA^­) were reduced whereas CD8 EM (CCR7^­/45RA^­) and TD (CCR7^­/45RA⁺) lymphocytes were increased; activated CD4 (25⁺) and CD8 (RO/38⁺) were increased; double positive (3⁺/4⁺/8⁺/1a⁺) lymphocytes were increased. All these differences were statistically significant. Finally, interferon-g (IFN-γ)-specific mRNA was increased in sero-reverters, whereas APOBEC3G and 3F and TRIM-specific mRNA were comparable in all groups of adolescents analyzed.

Conclusions:  Immune activation and a skewing of the maturative CD8 pathway favoring the most differentiated, perforin-enriched cells is detected in sero-reverter healthy adolescents born of HIV⁺ mothers. In contrast, the expression of the main endogenous antivirals is similar in all groups analyzed. These data suggest that in utero exposure to HIV or to viral particles results in a long-lasting imprinting on the immune system. Alternatively, it could be speculated that an immune response that is naturally more prone to activation and to stronger effector mechanisms could be associated with prevention of vertical HIV infection.