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The Journal of Immunology, 2006, 177: 5647-5651.
Copyright © 2006 by The American Association of Immunologists, Inc.

Bacillus Calmette Guerin Vaccination of Human Newborns Induces a Specific, Functional CD8+ T Cell Response1

Rose Ann Murray*, Nazma Mansoor{dagger}, Ryhor Harbacheuski*, Jorge Soler*, Virginia Davids{dagger}, Andreia Soares{dagger}, Anthony Hawkridge{dagger}, Gregory D. Hussey{dagger}, Holden Maecker{ddagger}, Gilla Kaplan* and Willem A. Hanekom2,{dagger}

* Public Health Research Institute, Newark, NJ 07103; {dagger} South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and {ddagger} BD Biosciences, San Jose, CA 95131

Mounting evidence points to CD8+ T cells playing an important role in protective immunity against Mycobacterium tuberculosis. The only available vaccine against tuberculosis, bacillus Calmette Guérin (BCG), has traditionally been viewed not to induce these cells optimally. In this study, we show that vaccination of human newborns with BCG does indeed induce a specific CD8+ T cell response. These cells degranulated or secreted IFN-{gamma}, but not both, when infant blood was incubated with BCG. This stimulation also resulted in proliferation and up-regulation of cytotoxic molecules. Overall, the specific CD8+ T cell response was quantitatively smaller than the BCG-induced CD4+ T cell response. Incubation of whole blood with M. tuberculosis also caused CD8+ T cell IFN-{gamma} expression. We conclude that BCG induces a robust CD8+ T cell response, which may contribute to vaccination-induced protection against tuberculosis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 W.A.H. is supported by the National Institutes of Health Grant (NIH) AI 065653, the Dana Foundation, the European and Developing Countries Trials Partnership, and the Aeras Global Tuberculosis Vaccine Foundation. G.K. is supported by NIH Grants AI 054361 and AI 22616, and by the Heiser Foundation.

2 Address correspondence and reprint requests to Dr. Willem A. Hanekom, South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, Wernher Beit S2.01, University of Cape Town Health Sciences Faculty, Anzio Road, Observatory, 7925 Cape Town, South Africa. E-mail address: Willem{at}rmh.uct.ac.za

3 Abbreviations used in this paper: BCG, Bacille Calmette Guérin; WB-ICC, whole blood intracellular cytokine assay; MOI, multiplicity of infection; SEB, staphylococcal enterotoxin B.




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