Abstract
Objective: The majority of infants born, in developed countries, to HIV-1 positive women are exposed to the HIV-1 virus in utero or peri/post-partum, but are born uninfected. We, and others, have previously shown HIV-1 specific T cell responses in HIV-1 exposed seronegative (HESN) neonates/infants. Our objective in this study was to examine the rate of decay in their HIV-1 specific T cell response over time from birth. Design: Cross-sectional and longitudinal studies of HIV-1 specific T cell responses in HESN infants were performed. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 18 HIV-1 DNA PCR negative infants born to HIV-1 infected mothers receiving care at the Jacobi Medical Center, Bronx, NY, USA. PBMC were examined for T cell responses to HIV-1 antigens by interferon-gamma (IFN-γ) ELISPOT. Results: PBMC from 15 HESN neonates/infants were analyzed. We observed a decay of HIV-1 specific T cell responses from birth at a rate of −0.599 spot forming unit/106 cells per day, with a median half-life decay rate of 21.38 weeks (13.39–115.8). Conclusion: Our results support the dynamic nature of T cell immunity in the context of a developing immune system. The disparate rate of decay with studies of adults placed on antiretroviral drugs suggests that antigen specific T cell responses are driven by the natural rate of decay of the T cell sub-populations themselves.
Highlights
Uninfected infants born to HIV-1 infected mothers (HESN infants) could provide valuable insight into the kinetics of HIV-1 specific T cell responses in exposed uninfected individuals
We found that HIV-1 specific antigen responses were stronger and broader in HIV-1 exposed seronegative (HESN) neonates/infants at the time nearest to birth, and decayed both in magnitude and breadth as time from birth progressed
We contend that the decay in the magnitude and breadth of HIV-1 antigen specific immune response in these HESN infants is due to the absence of viral antigens, we cannot rule out an effect from postpartum ZDV exposure, or the emergence of a regulatory immune cell population, which might suppress HIV-1 specific immune responses
Summary
Several reports, including from our group, have identified HIV-1 specific T cell responses in HIV-1 Exposed Seronegative (HESN) infants born to HIV-1 infected mothers (Cheynier et al, 1992; Rowland-Jones et al, 1993; Aldhous et al, 1994; De Maria et al, 1994; Kuhn et al, 2001; Legrand et al, 2006). Despite efforts to control maternal viral load, pregnant, or breast-feeding mothers, may experience fluctuations in viremia (Van Sighem et al, 2008) These periods of variable viral load pose an increased risk of exposure to and vertical transmission of HIV-1 during pregnancy, peripartum, and post-partum (Rowland-Jones et al, 1993; Kuhn et al, 2001; Sabbaj et al, 2002, 2005; Sharp et al, 2005; John-Stewart et al, 2009; Walter et al, 2009). Uninfected infants born to HIV-1 infected mothers (HESN infants) could provide valuable insight into the kinetics of HIV-1 specific T cell responses in exposed uninfected individuals
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