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

Patricia L Semple,Marcia Watkins,Willem A Hanekom,Gilla Kaplan,Stanley Ress,Alan M Krensky,Virginia Davids

doi:10.1155/2011/438463

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.

Highlights

It is estimated that approximately one third of the world’s population is infected with Mycobacterium tuberculosis (M.tb) resulting in about 1.7 million deaths from tuberculosis (TB) annually [1]
We have evaluated expression of the cytolytic mediators perforin and granulysin in both CD56+ Natural Killer (NK) cells and in CD4+ and CD8+ T-cell subsets in cord blood mononuclear cells (CBMCs) and observed that (i) intrinsic expression of cytolytic mediators was limited to CD56+ cells and not found in CD4+ and CD8+ T-cells and (ii) induction of perforin and granulysin expression in cord blood T-cells occurred selectively in response to in vitro stimulation with Bacilli Calmette-Guerin (BCG), but not purified protein derivative of tuberculin (PPD)
In 10-week-old BCG-vaccinated infants, upregulation of perforin and granulysin expression in CD4+ and CD8+ T-cell was demonstrable in response to both BCG and PPD stimulation

Summary

Introduction

It is estimated that approximately one third of the world’s population is infected with Mycobacterium tuberculosis (M.tb) resulting in about 1.7 million deaths from tuberculosis (TB) annually [1]. It has been suggested that the strain of BCG and the route of administration may affect the efficacy of the vaccine [5,6,7,8] as well as determine the nature of the antigenspecific T-cell responses [9]. While vaccination at birth with Mycobacterium bovis Bacilli Calmette-Guerin (BCG) protects against severe childhood tuberculosis, there is no consensus as to which components of the BCG-induced immune response mediate this protection. 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

Objectives

Methods

Conclusion