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Infection and Immunity, August 2005, p. 4913-4921, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4913-4921.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

NK Cells Help To Induce CD8+-T-Cell Immunity against Toxoplasma gondii in the Absence of CD4+ T Cells

Crescent L. Combe,1 Tyler J. Curiel,2 Magali M. Moretto,1 and Imtiaz A. Khan1*

Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana,1 Department of Hematology and Medical Oncology, Tulane University School of Medicine, New Orleans, Louisiana2

Received 10 February 2005/ Returned for modification 23 March 2005/ Accepted 7 April 2005

CD8+ T-cell immunity plays an important role in protection against intracellular infections. Earlier studies have shown that CD4+ T-cell help was needed for launching in vivo CD8+ T-cell activity against these pathogens and tumors. However, recently CD4+ T-cell-independent CD8 responses during several microbial infections including those with Toxoplasma gondii have been described, although the mechanism is not understood. We now demonstrate that, in the absence of CD4+ T cells, T. gondii-infected mice exhibit an extended NK cell response, which is mediated by continued interleukin-12 (IL-12) secretion. This prolonged NK cell response is critical for priming parasite-specific CD8+ T-cell immunity. Depletion of NK cells inhibited the generation of CD8+ T-cell immunity in CD4–/– mice. Similarly neutralization of IL-12 reduces NK cell numbers in infected animals and leads to the down-regulation of CD8+ T-cell immunity against T. gondii. Adoptive transfer of NK cells into the IL-12-depleted animals restored their CD8+ T-cell immune response, and animals exhibited reduced mortality. NK cell gamma interferon was essential for cytotoxic T-lymphocyte priming. Our studies for the first time demonstrate that, in the absence of CD4+ T cells, NK cells can play an important role in induction of primary CD8+ T-cell immunity against an intracellular infection. These observations have therapeutic implications for immunocompromised individuals, including those with human immunodeficiency virus infection.

* Corresponding author. Mailing address: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112. Phone: (504) 568-6116. Fax: (504) 568-2918. E-mail: ikhan{at}lsuhsc.edu.

Editor: J. F. Urban, Jr.

Infection and Immunity, August 2005, p. 4913-4921, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4913-4921.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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