Functional properties of the T cell receptor repertoire in responding to the protective domain of heat-shock protein 60 from Histoplasma capsulatum.
Cells expressing the T cell receptor beta-chain variable region (Vbeta) 6 constitute the majority of T cells responding to the protective domain (F3) of heat-shock protein 60 from Histoplasma capsulatum. This subset of cells exhibits a T helper type 1 (Th1) profile and is pivotal in protection. In this study, additional F3-reactive T cell lines were generated, leading to the discovery of a Th2 line. Vbeta usage by clones was more diverse than has been previously recognized. Nearly all Th2 clones expressed Vbeta8.1/8.2, whereas Th1 clones expressed Vbeta11 or Vbeta6. In adoptive transfer studies, only the Vbeta6(+) Th1 clone prolonged survival; all Th2 clones accelerated mortality. The ameliorative effect of the Vbeta6(+) Th1 clone was abrogated by treatment with monoclonal antibody to interferon-gamma. Neutralization of interleukin-4 reversed the shortened survival of mice to which the Vbeta6(+) Th2 clone was administered. Thus, F3-mediated protection is confined to a defined Vbeta population, but exacerbation of disease is mediated by multiple Vbeta families.
Veterans Affairs Hospital and Department of Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, USA. george.deepe@uc.edu
George S
GS
Deepe
Reta S
RS
Gibbons
D019264:Adoptive Transfer; D000818:Animals; D018834:Chaperonin 60 / Q000737:chemistry* / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D006658:Histoplasma / Q000276:immunology* / Q000472:pathogenicity; D006660:Histoplasmosis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D018834:Chaperonin 60; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta