The protective immune response to heat shock protein 60 of Histoplasma capsulatum is mediated by a subset of V beta 8.1/8.2+ T cells

• Published in: The Journal of immunology (1950) Vol. 169; no. 10; pp. 5818 - 5826
• Main Authors: Scheckelhoff, Mark, Deepe, Jr, George S
• Format: Journal Article
• Language: English
• Published: United States 15.11.2002
• Subjects: Animals; Cell Line; Chaperonin 60 - administration & dosage; Chaperonin 60 - genetics; Chaperonin 60 - immunology; Clone Cells - immunology; Clone Cells - metabolism; Clone Cells - microbiology; Clone Cells - transplantation; Cytokines - biosynthesis; Fungal Vaccines - administration & dosage; Fungal Vaccines - immunology; Histoplasma - genetics; Histoplasma - immunology; Histoplasmosis - immunology; Histoplasmosis - microbiology; Histoplasmosis - prevention & control; Immunoglobulin Variable Region - analysis; Immunoglobulin Variable Region - biosynthesis; Immunotherapy, Adoptive - methods; Lymphocyte Depletion; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Receptors, Antigen, T-Cell, alpha-beta - administration & dosage; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - deficiency; Receptors, Antigen, T-Cell, alpha-beta - physiology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - microbiology; T-Lymphocyte Subsets - transplantation; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.169.10.5818

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 Vbeta usage by flow cytometry and RT-PCR. Vbeta8.1/8.2(+) T cells were preferentially expanded; other clones bore Vbeta4, -6, or -11. When Vbeta8.1/8.2(+) cells were depleted in mice, Vbeta4(+) T cell clones were almost exclusively isolated. Measurement of cytokine production demonstrated that nine of 16 Vbeta8.1/8.2(+) clones were Th1, while only three of 13 non-Vbeta8.1/8.2(+) clones were Th1. In mice immunized with rHsp60, depletion of Vbeta8.1/8.2(+), but not Vbeta6(+) plus Vbeta7(+), T cells completely abolished the protective efficacy of Hsp60 to lethal and sublethal challenges. Examination of the TCR revealed that a subset of Vbeta8.1/2(+) clones that produced IFN-gamma and were reactive to F3 shared a common CDR3 sequence, DGGQG. Transfer of these T cell clones into TCR alpha/beta(-/-) or IFN-gamma(-/-) mice significantly improved survival, while transfer of other Vbeta8.1/8.2(+) 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 Vbeta8.1/8.2(+) T cells is crucial for the generation of a protective response to rHsp60.