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Clinical and Vaccine Immunology, November 2008, p. 1666-1673, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00202-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Exposure of Cord Blood to Mycobacterium bovis BCG Induces an Innate Response but Not a T-Cell Cytokine Response {triangledown}

M. L. V. Watkins,1,5 P. L. Semple,1 B. Abel,2,3 W. A. Hanekom,2,3 G. Kaplan,6 and S. R. Ress1,4*

Division of Clinical Immunology, Department of Medicine,1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine,2 School of Child and Adolescent Medicine, University of Cape Town, Cape Town, South Africa,3 Groote Schuur Hospital, Cape Town, South Africa,4 National Health Laboratory Service, Cape Town, South Africa,5 Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey6

Received 2 June 2008/ Returned for modification 3 July 2008/ Accepted 9 September 2008

Despite routine vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) soon after birth, tuberculosis in babies and adults remains epidemic in South Africa. The immune responses of the naïve newborn child and how they are affected by vaccination with BCG are as yet not fully understood. Immunity during pregnancy and in healthy human newborns may be skewed toward type 2 cytokine production; however, it is type 1 cytokines that are required for protection against M. tuberculosis infection. To better understand neonatal cytokine responses prior to and following exposure to mycobacteria, we have collected cord blood and peripheral blood samples and evaluated the cytokine response following ex vivo incubation with BCG. Gamma interferon (IFN-{gamma}), interleukin 10 (IL-10), IL-12, and low levels of IL-13 and IL-5 but no IL-4 were secreted into the culture supernatant of cord blood mononuclear cells. Intracellular staining showed that IL-10 and IL-12 were produced by monocytes and that IFN-{gamma} was produced by natural killer (NK) cells but not by CD4+ or CD8+ T cells. In contrast, in the peripheral blood samples collected from babies 13 weeks post-BCG vaccination, IFN-{gamma} was detected within CD4+ and CD8+ cells. Taken together, the data suggest a central role for Th1 cytokines in naïve as well as BCG-vaccinated neonates in the protective immune response to tuberculosis. NK cell-derived IFN-{gamma} produced in naïve neonates likely plays a key protective role via monocyte activation and the priming of a subsequent adaptive Th1 response.

* Corresponding author. Mailing address: Division of Clinical Immunology, Department of Medicine, Groote Schuur Hospital, H47 Old Main Building, Cape Town 7925, South Africa. Phone: 2721-4066201. Fax: 2721-4486815. E-mail: stan.ress{at}uct.ac.za

{triangledown} Published ahead of print on 24 September 2008.

Clinical and Vaccine Immunology, November 2008, p. 1666-1673, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00202-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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