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Clinical and Developmental Immunology
Volume 2011 (2011), Article ID 438463, 10 pages
http://dx.doi.org/10.1155/2011/438463
Research Article

Induction of Granulysin and Perforin Cytolytic Mediator Expression in 10-Week-Old Infants Vaccinated with BCG at Birth

1Division of Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town 7925, South Africa
2National Health Laboratory Service, Cape Town 8000, South Africa
3South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town 7700, South Africa
4National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-8322, USA
5School of Child and Adolescent Medicine, University of Cape Town, Cape Town, South Africa
6Laboratory of Mycobacterial Immunity and Pathogenesis, Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-3535, USA
7Groote Schuur Hospital, Cape Town 7925, South Africa

Received 16 August 2010; Accepted 27 October 2010

Academic Editor: James Triccas

Copyright © 2011 Patricia L. Semple et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. While vaccination at birth with Mycobacterium bovis Bacilli Calmette-Guérin (BCG) protects against severe childhood tuberculosis, there is no consensus as to which components of the BCG-induced immune response mediate this protection. However, granulysin and perforin, found in the granules of cytotoxic T lymphocytes and Natural Killer (NK) cells, can kill intracellular mycobacteria and are implicated in protection against Mycobacterium tuberculosis. Methods. We compared the cellular expression of granulysin and perforin cytolytic molecules in cord blood and peripheral blood from 10-week-old infants vaccinated at birth with either Japanese or Danish BCG, administered either intradermally or percutaneously. Results. In cord blood, only CD56+ NK cells expressed granulysin and perforin constitutively. These cytolytic mediators were upregulated in CD4+ and CD8+ cord blood cells by ex vivo stimulation with BCG but not with PPD. Following BCG vaccination of neonates, both BCG and PPD induced increased expression of granulysin and perforin by CD4+ and CD8+ T cells. There was no difference in expression of cytolytic molecules according to vaccination route or strain. Conclusions. Constitutive expression of perforin and granulysin by cord blood NK-cells likely provides innate immunity, while BCG vaccination-induced expression of these cytolytic mediators may contribute towards protection of the neonate against tuberculosis.