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Infection and Immunity, December 2001, p. 7213-7223, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7213-7223.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Exaggerated Proinflammatory and Th1 Responses in the Absence of gamma /delta T Cells after Infection with Listeria monocytogenes

Marianne J. Skeen, Emily P. Rix, Molly M. Freeman, and H. Kirk Ziegler*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 15 March 2001/Returned for modification 14 May 2001/Accepted 22 August 2001

While gamma /delta T cells are involved in host defense and immunopathology in a variety of infectious diseases, their precise role is not yet clearly defined. In the absence of gamma /delta T cells, mice die after infection with a dose of Listeria monocytogenes that is not lethal in immunologically intact animals. Morbidity might result from insufficient levels of cytokines normally produced by gamma /delta T cells or conversely from an excess of cytokines due to a lack of down-regulation of the inflammatory response in the absence of gamma /delta T cells. Consistent with a regulatory role, we found that systemic levels of proinflammatory cytokines (interleukin-6 [IL-6], IL-12, and gamma interferon [IFN-gamma ]) were significantly higher in the absence of gamma /delta T cells during the innate phase of the response. Using combinations of genetically altered and immunodepleted mice, we found evidence for gamma /delta T-cell-mediated regulation of IFN-gamma production by multiple cell types of both lymphoid and myeloid lineages. The antigen-specific alpha /beta T-cell response that followed the exaggerated innate response was also increased in gamma /delta T-cell-deficient mice. These findings are consistent with an emerging picture from a variety of immune response models of a critical role for gamma /delta T cells in down-modulation of the immune response.

* Corresponding author. Mailing address: Emory University, Department of Microbiology and Immunology, 1510 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-5974. Fax: (404) 727-9140. E-mail: ziegler{at}microbio.emory.edu.

Infection and Immunity, December 2001, p. 7213-7223, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7213-7223.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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