In-utero infection with HIV-1 associated with suppressed lymphoproliferative responses at birth.
In-utero exposure to HIV-1 may affect the immune system of the developing child and may induce HIV-1-specific immune responses, even in the absence of HIV-1 infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1-uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired HIV-1 in utero. Cord blood mononuclear cells were assayed using [(3) H]-thymidine incorporation for proliferation in response to HIV-1 p55-gag and the control stimuli phytohaemagglutinin (PHA), Staphylococcus enterotoxin B (SEB) and allogeneic cells. In response to HIV-1 p55-gag, eight (20%) HIV-1-exposed, uninfected (EU) infants had a stimulation index (SI) ≥ 2 and three (30%) in-utero HIV-1 infected infants had SI ≥2. The frequency and magnitude of responses to HIV-1 p55-gag were low overall, and did not differ statistically between groups. However, proliferative responses to control stimuli were significantly higher in EU infants than in infants infected in utero, with a median SI in response to PHA of 123 [interquartile range (IQR) 77-231] versus 18 (IQR 4-86) between EU and infected infants, respectively (P < 0·001). Among infected infants, gestational maturity was associated with the strength of HIV-1 p55-gag response (P < 0·001); neither maternal nor infant HIV-1 viral load was associated. In summary, EU and HIV-1-infected infants mounted HIV-1-specific lymphoproliferative responses at similar rates (20-30%), and although global immune function was preserved among EU infants, neonatal immune responses were significantly compromised by HIV-1 infection. Such early lymphoproliferative compromise may, in part, explain rapid progression to AIDS and death among HIV-1-infected infants.
Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya; Department of Medicine, University of Washington, Seattle, Washington, USA; Department of Global Health, University of Washington, Seattle, Washington, USA.
B
B
Lohman-Payne
T
T
Sandifer
M
M
OhAinle
C
C
Crudder
J
J
Lynch
M M
MM
Omenda
J
J
Maroa
K
K
Fowke
G C
GC
John-Stewart
C
C
Farquhar
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D000328:Adult; D049109:Cell Proliferation; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000821:virology
Candida; SEB; allogenic; gestational age; p55gag