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, beta(2)-microglobulin (beta(2)-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 beta(2)-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.
Schramm
Diana B
DB
AIDS Virus Research Unit, National Institute for Communicable Diseases, Department of Virology, University of the Witwatersrand, Gauteng, South Africa.
Meddows-Taylor
Stephen
S
Gray
Glenda E
GE
Kuhn
Louise
L
Tiemessen
Caroline T
CT
D000328:Adult; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007112:Immunity, Maternally-Acquired / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D011446:Prospective Studies; D019562:Viral Load
D000939:Epitopes; D015488:HIV Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor