CD4 and CD8 T-cell responses to mycobacterial antigens in African children.
BACKGROUND
The current tuberculosis (TB) vaccine, bacille Calmette-Guérin (BCG), does not provide adequate protection against TB disease in children. Furthermore, more efficacious TB vaccines are needed for children with immunodeficiencies such as HIV infection, who are at highest risk of disease.


OBJECTIVE
To characterize mycobacteria-specific T cells in children who might benefit from vaccination against TB, focusing on responses to antigens contained in novel TB vaccines.


METHODS
Whole blood was collected from three groups of BCG-vaccinated children: HIV-seronegative children receiving TB treatment (n = 30), HIV-infected children (n = 30), and HIV-unexposed healthy children (n = 30). Blood was stimulated with Ag85B and TB10.4, or purified protein derivative, and T-cell cytokine production by CD4 and CD8 was determined by flow cytometry. The memory phenotype of antigen-specific CD4 and CD8 T cells was also determined.


RESULTS
Mycobacteria-specific CD4 and CD8 T-cell responses were detectable in all three groups of children. Children receiving TB treatment had significantly higher frequencies of antigen-specific CD4 T cells compared with HIV-infected children (P = 0.0176). No significant differences in magnitude, function, or phenotype of specific T cells were observed in HIV-infected children compared with healthy control subjects. CD4 T cells expressing IFN-gamma, IL-2, or both expressed a CD45RA(-)CCR7(-)CD27(+/-) effector memory phenotype. Mycobacteria-specific CD8 T cells expressed mostly IFN-gamma in all groups of children; these cells expressed CD45RA(-)CCR7(-)CD27(+/-) or CD45RA(+)CCR7(-)CD27(+/-) effector memory phenotypes.


CONCLUSIONS
Mycobacteria-specific T-cell responses could be demonstrated in all groups of children, suggesting that the responses could be boosted by new TB vaccines currently in clinical trials.
Institute of Infectious Diseases and Molecular Medicine, South African Tuberculosis Vaccine Initiative, and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Nontobeko G
NG
Tena-Coki
Thomas J
TJ
Scriba
Nomathemba
N
Peteni
Brian
B
Eley
Robert J
RJ
Wilkinson
Peter
P
Andersen
Willem A
WA
Hanekom
Beate
B
Kampmann
D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D044383:Black People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007223:Infant; D008297:Male; D013019:South Africa; D014376:Tuberculosis / Q000150:complications / Q000276:immunology* / Q000517:prevention & control
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016207:Cytokines