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Cutting Edge: IFN--Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis¹

Ian Justin Glomski^*,, Jean-Philippe Corre^*,, Michèle Mock^*, and Pierre Louis Goossens^2,*,

^* Institut Pasteur, Unité des Toxines et Pathogénie Bactérienne, Paris, France; and Centre National de la Recherche Scientifique, Unité de Recherche Associée 2172, Paris, France

Virulent strains of Bacillus anthracis produce immunomodulating toxins and an antiphagocytic capsule. The toxin component-protective Ag is a key target of the antianthrax immune response that induces production of toxin-neutralizing Abs. Coimmunization with spores enhances the antitoxin vaccine, and inactivated spores alone confer measurable protection. We aimed to identify the mechanisms of protection induced in inactivated-spore immunized mice that function independently of the toxin/antitoxin vaccine system. This goal was addressed with humoral and CD4 T lymphocyte transfer, in vivo depletion of CD4 T lymphocytes and IFN-, and Ab-deficient (µMT^–/–) or IFN--insensitive (IFN-R^–/–) mice. We found that humoral immunity did not protect from nontoxinogenic capsulated bacteria, whereas a cellular immune response by IFN--producing CD4 T lymphocytes protected mice. These results are the first evidence of protective cellular immunity against capsulated B. anthracis and suggest that future antianthrax vaccines should strive to augment cellular adaptive immunity.

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 This study was supported in part by a Judith P. Sulzberger Post-Doctoral Fellowship from Pasteur Foundation of New York (to I.J.G.).

² Address correspondence and reprint requests to Dr. Pierre Louis Goossens, Unité des Toxines et Pathogénie Bactérienne, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. E-mail address: pierre.goossens{at}pasteur.fr

³ Abbreviations used in this paper: LT, lethal toxin; PA, protective Ag; Th1, Th lymphocyte type-1; FIS, formaldehyde-inactivated spore; BMDM, bone marrow-derived macrophage.

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