Low Maternal Viral Loads and Reduced Granulocyte-Macrophage Colony-Stimulating Factor Levels Characterize Exposed, Uninfected Infants Who Develop Protective Human Immunodeficiency Virus Type 1-Specific Responses

Human immunodeficiency virus type 1 (HIV-1)-specific cellular immune responses are elicited in a proportion of infants born to HIV-1-infected mothers and are associated with protection against vertical transmission. To investigate correlates of these HIV-1-specific responses, we examined levels of the immune activation markers neopterin, β2 -microglobulin (β2 -m), and solublel -selectin (sl -selectin); the immunomodulatory and hematopoietic factors interleukin-7 (IL-7), stromal-cell-derived factor 1 alpha (CXCL12), and granulocyte-macrophage colony-stimulating factor (GM-CSF); and the immunoregulatory cytokine IL-10 among a group of newborns born to HIV-1-positive mothers who did not receive any antiretroviral drugs for prevention of perinatal HIV-1 transmission. Cellular immune responses to HIV-1 envelope (Env) peptides were also measured. We aimed to determine whether newborns who elicit HIV-1-specific cellular immune responses (Env+ ) and those who lack these responses (Env− ) exhibit unique immune features. Our data confirmed that no Env+ infants acquired HIV-1 infection. Among exposed, uninfected infants, Env+ infants had reduced immune activation (as measured by β2 -m and sl -selectin levels in cord blood plasma) compared to Env− infants as well as reduced GM-CSF levels in cord blood plasma. There was also a reduced ability of cord blood mononuclear cells to be induced to produce GM-CSF among Env+ infants. Maternal viral load was lower in Env+ infants, suggesting that exposure to low levels of antigen may be responsible for priming the protective responses. These findings suggest that infants who are able to develop apparently protective HIV-1-specific cellular immune responses have immunological features and viral exposure histories that distinguish them from their nonresponder counterparts, providing new insights into the development of HIV-1 protective immunity.