Gamma interferon production in response to Mycobacterium bovis BCG and Mycobacterium tuberculosis antigens in infants born to human immunodeficiency virus-infected mothers.
In utero sensitization to infectious pathogens can establish immunological memory and may influence the immune response to unrelated antigens. Little is known about the influence of intrauterine human immunodeficiency virus (HIV) exposure on the cellular immune response to mycobacterial antigens. Whole-blood culture gamma interferon (IFN-gamma) production in response to mycobacterial antigens was measured at birth and 6 weeks of age to determine the characteristics of the IFN-gamma response in HIV-exposed infants to Mycobacterium bovis BCG and mycobacterial antigens. At birth, we observed an increased immune activation in response to phytohemagglutinin among HIV-exposed, uninfected infants. In a proportion of these infants, we also observed an increased immune activation in response to purified protein derivative, BCG, and early secreted antigen target 6. Increases in the IFN-gamma response to the four antigens between birth and 6 weeks of age, observed in all HIV-unexposed infants, was absent in a substantial proportion of HIV-exposed, uninfected infants. The immunological differences persisted at 6 weeks of age, suggesting a sustained impact of in utero immune priming by HIV. Intrauterine exposure to HIV affects the infants' cellular immune response to mycobacterial antigens, either specifically or as a consequence of nonspecific, broadly reactive immune activation. Further studies will be important to help determine optimal vaccination and disease prevention strategies for this vulnerable population group.
Department of Epidemiology, The University of North Carolina at Chapel Hill, 2104F McGavran Greenberg Hall, Chapel Hill, NC 27599-7435, USA. vanrie@email.unc.edu
Annelies
A
Van Rie
Shabir A
SA
Madhi
Jayvant R
JR
Heera
Stephen
S
Meddows-Taylor
Aaron M
AM
Wendelboe
Fiona
F
Anthony
Avy
A
Violari
Caroline T
CT
Tiemessen
D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis*; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D007371:Interferon-gamma