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8.1/8.2+ T Cells1
* Department of Molecular Genetics, Biochemistry, and Microbiology, and
Veterans Affairs Hospital and Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267
Immunization with recombinant heat shock protein 60 (rHsp60) from
Histoplasma capsulatum or a region of the protein
designated fragment 3 (F3) confers protection from a subsequent
challenge in mice. To determine the T cell repertoire involved in the
response to Hsp60, T cell clones from C57BL/6 mice immunized with
rHsp60 were generated and examined for V
usage by flow cytometry and
RT-PCR. V8.1/8.2+ T cells were preferentially expanded;
other clones bore V4, -6, or -11. When V8.1/8.2+
cells were depleted in mice, V4+ T cell clones were
almost exclusively isolated. Measurement of cytokine production
demonstrated that nine of 16 V8.1/8.2+ clones were Th1,
while only three of 13 non-V8.1/8.2+ clones were Th1. In
mice immunized with rHsp60, depletion of V8.1/8.2+, but
not V6+ plus V7+, T cells completely
abolished the protective efficacy of Hsp60 to lethal and sublethal
challenges. Examination of the TCR revealed that a subset of
V8.1/2+ clones that produced IFN-
and were reactive
to F3 shared a common CDR3 sequence, DGGQG. Transfer of these T cell
clones into TCR 
/-/- or IFN--/-
mice significantly improved survival, while transfer of other
V8.1/8.2+ clones that were F3 reactive but were Th2 or
clones that were not reactive to F3 but were Th1 did not confer
protection. These data indicate that a distinct subset of
V8.1/8.2+ T cells is crucial for the generation of a
protective response to rHsp60.
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