Identification of human immunodeficiency virus-1 specific CD8+ and CD4+ T cell responses in perinatally-infected infants and their mothers.
BACKGROUND
There are few data describing the specificity, breadth and magnitude of T cell responses to HIV-1 in infancy.


METHODS
HIV-specific CD8+ and CD4+ T cell responses to peptide pools representing Gag, Env, Pol, Nef and the regulatory regions (Reg) were simultaneously measured in 18 perinatally-infected infants and 14 of their chronically-infected mothers, using a whole blood interleukin-2 and interferon-gamma flow cytometric intracellular cytokine staining assay.


RESULTS
HIV-specific CD8+ T cell responses were detected in all the infants aged 6 weeks and older (range 0.1-6.62%) and their mothers (range 0.1-4.89%). HIV-specific CD4+ T cell responses were detected in 33% of the infants (range 0.11-0.54%) and 73% of the mothers (range 0.16-0.84). CD8+ T cell responses in the mothers were almost equally spread between the variable (Nef, Reg and Env) and conserved proteins (Gag and Pol). Conversely, CD8+ T cell responses to the more variable proteins dominated in the perinatally-infected infants comprising 74% of the total response. Interestingly, mothers and infants shared responses to at least one peptide pool, whereas only one mother-infant pair shared a peptide pool targeted by CD4+ T cells. Two in-utero-infected infants tested at birth had CD8+ T cell responses, and one of them had an Env-specific CD4 T cell response.


CONCLUSIONS
Our observations that HIV-specific CD8+ and CD4+ T cell responses can be detected in perinatally-infected infants from 6 weeks of age and that CD8+ T cell responses predominantly target the variable proteins have important implications for HIV vaccine design.
Shalekoff
Sharon
S
AIDS Virus Research Unit, National Institute for Communicable Diseases, Sandringham 2131, South Africa.
Meddows-Taylor
Stephen
S
Gray
Glenda E
GE
Sherman
Gayle G
GG
Coovadia
Ashraf H
AH
Kuhn
Louise
L
Tiemessen
Caroline T
CT
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011247:Pregnancy / Q000276:immunology; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000276:immunology* / Q000821:virology
D016207:Cytokines