Functional properties of the T cell receptor repertoire in responding to the protective domain of heat-shock protein 60 from Histoplasma capsulatum.

Abstract

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.