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Clinical and Vaccine Immunology, April 2007, p. 348-354, Vol. 14, No. 4
1071-412X/07/$08.00+0     doi:10.1128/CVI.00464-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Gauteng, South Africa,¹ Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa,² Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York³

Received 14 December 2006/ Returned for modification 16 January 2007/ Accepted 1 February 2007

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, ß₂-microglobulin (ß₂-m), and soluble L-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 ß₂-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.

Published ahead of print on 14 February 2007.