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.
Deepe
George S
GS
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
Gibbons
Reta S
RS
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