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Infection and Immunity, April 2005, p. 2129-2134, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2129-2134.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Deficiency in Gamma Interferon or Interleukin-10 Modulates T-Cell-Dependent Responses to Heat Shock Protein 60 from Histoplasma capsulatum

Mark Scheckelhoff^1,2, and George S. Deepe Jr.^2,3*

Department of Molecular Genetics, Biochemistry, and Microbiology,¹ Division of Infectious Diseases,² Veterans Affairs Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio³

Received 15 November 2004/ Returned for modification 7 December 2004/ Accepted 10 December 2004

Immunization of mice with heat shock protein 60 from Histoplasma capsulatum or a polypeptide from the protein designated F3 confers protection. Vß8.1/8.2⁺ T cells are critically important for the protective efficacy of this antigen. The production of interleukin-10 and gamma interferon following vaccination is essential for efficacy. In this study, we sought to determine whether the absence of either cytokine modified the repertoire of antigen-reactive T cells and whether it altered the functional properties of T cells. Mice lacking gamma interferon or interleukin-10 manifested a skewed repertoire compared to that of wild-type mice. The bias was most marked in gamma interferon-deficient mice and modestly altered in interleukin-10-deficient animals. The altered repertoire in gamma interferon-deficient mice could not be explained at the level of antigen presentation or by the absence of this population from mice. The proportion of T cells from interleukin-10-deficient mice manifesting a Th1 phenotype was greatly increased compared to that from wild-type animals. Transfer of splenocytes from gamma interferon- or interleukin-10-deficient mice immunized with heat shock protein 60 failed to confer protection in T-cell receptor /ß^–/– mice. The transfer of T-cell clones that did not produce both cytokines failed to prolong survival in T-cell receptor /ß^–/– mice, whereas the clones with the same features that were derived from wild-type mice did. These results indicate that the cytokine milieu influences the shape of the T-cell receptor repertoire and support the importance of gamma interferon and interleukin-10 in the efficacy of heat shock protein 60.

Editor: T. R. Kozel

Present address: Tupper Research Institute, Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111.

This article has been cited by other articles:

• de Bastos Ascenco Soares, R., Gomez, F. J., de Almeida Soares, C. M., Deepe, G. S. Jr. (2008). Vaccination with Heat Shock Protein 60 Induces a Protective Immune Response against Experimental Paracoccidioides brasiliensis Pulmonary Infection. Infect. Immun. 76: 4214-4221 [Abstract] [Full Text]