Vβ4+ T cells promote clearance of infection in murine pulmonary histoplasmosis

Abstract

T cells are essential for controlling infection with Histoplasma capsulatum. Because the T cell receptor is vital for transducing the biological activities of these cells, we sought to determine if exposure to this fungus induced an alteration in the Vβ repertoire in lungs of C57BL/6 mice infected intranasally. Vβ2+ cells were elevated on day 3 after infection; Vβ4+ cells were higher than controls on days 7, 10, and 14 after infection. Vβ10+ cells were increased on days 14 and 21, and Vβ11+ exceeded controls only on day 14. We investigated the clonality and function of Vβ4+ cells because their expansion transpired during the critical time of infection, that is, when cellular immunity is activated. Sequence analysis demonstrated preferential use of a restricted set of sequences in the complementarity-determining region 3. Elimination of Vβ4+ cells from mice impaired their ability to resolve infection. In contrast, depletion of Vβ7+ cells, the abundance of which was similar to that of Vβ4+, did not alter elimination of the fungus. The identification of clonotypes of Vβ4+ cells suggests that a few antigenic determinants may drive proliferation of this subset, which is necessary for optimal clearance.