Cutting Edge: Unusual NK Cell Responses to HIV-1 Peptides Are Associated With Protection Against Maternal-Infant Transmission of HIV-1

Abstract

Listen

Translate article

Tiemessen CT, Shalekoff S, Meddows-Taylor S, et al. J Immunol. 2009;182(10):5914–5918PURPOSE OF THE STUDY. To investigate the role of specific T cell responses in maternal-fetal HIV-1 transmission.METHODS. CD3− cell responses to HIV-1 peptide were measured in HIV-infected mothers and their infants at birth and at 6 to 10 weeks after delivery. Samples from the mother-child cohort were stimulated with HIV-1 synthetic peptides in pools representing Gag, Pol, Nef, envelope, and regulatory protein regions. A positive peptide-induced CD3− response was defined as >3% of cells expressing cytokine at a level at least twofold above background levels. Additional HIV-infected women were recruited to determine whether CD3− HIV-responding cells expressed markers for B cells, monocytes, T cells, or natural killer (NK) cells.RESULTS. In the cohort of infected mothers, 54% and 22% had CD3− responses to envelope and regulatory peptides, respectively. These same regions were targeted to a lesser degree in their infants (21% and 5% had CD3− responses to envelope and regulatory peptides, respectively). Twenty-eight (57%) of 49 nontransmitting mothers and 13 (30%) of 44 exposed uninfected infants had detectable, HIV-specific, CD3− responses. In comparison, 1 (7%) of 15 transmitting mothers and 1 (6%) of 18 infected infants had these responses. When both the mother and the infant had HIV-specific CD3− responses, none of the infants became infected. One of the 22 responder mothers with a nonresponder infant transmitted HIV to her infant, and 2 of the nonresponder mothers with responder infants transmitted HIV to their infants. HIV-specific CD3− cells were identified as NK cells on the basis of cell surface markers.CONCLUSIONS. Mothers and infants who have CD3− NK cells that respond to HIV-1 peptides are substantially less likely to transmit and to acquire infection, respectively. CD3− NK cells respond with high specificity and strength to HIV-1 peptides from envelope and regulatory protein regions. This finding highlights the importance of innate immunity in preventing maternal-fetal transmission of HIV-1.REVIEWERS COMMENTS. Significant research has been conducted to find ways to reduce the risk of maternal-fetal transmission of HIV-1 infection. These interventions have been very successful, with transmission rates as low as 5% in developed countries. This article describes the immune responses seen in HIV-positive mothers and HIV-exposed infants and offers a possible marker for transmission risk. Although future studies need to be conducted, it is possible not only that this robust immune response to specific HIV-1 proteins may serve as a predictor of possible vertical transmission but also that a decrease in these cell numbers may serve as a marker of disease progression. In addition, the HIV-1-specific CD3− cell population may serve as a possible target for future immunotherapy for HIV infection.