A deficiency in gamma interferon or interleukin-10 modulates T-Cell-dependent responses to heat shock protein 60 from Histoplasma capsulatum.
Immunization of mice with heat shock protein 60 from Histoplasma capsulatum or a polypeptide from the protein designated F3 confers protection. Vbeta8.1/8.2+ 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 alpha/beta-/- mice. The transfer of T-cell clones that did not produce both cytokines failed to prolong survival in T-cell receptor alpha/beta-/- 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.
Scheckelhoff
Mark
M
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0560, USA.
Deepe
George S
GS
D000818:Animals; D017951:Antigen Presentation; D018834:Chaperonin 60 / Q000276:immunology*; D006658:Histoplasma / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D018834:Chaperonin 60; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D007371:Interferon-gamma