Vβ6+ and Vβ4+ T cells exert cooperative activity in clearance of secondary infection with Histoplasma capsulatum

We previously studied the lung V beta TCR repertoire of C57BL/6 mice during primary infection with the pathogen Histoplasma capsulatum, We observed a consistent oligoclonal expansion of V beta4(+) T cells during the peak of infection and early stages of resolution. The V beta4(+) family played a role in protective immunity against the fungus. Depletion of this subpopulation of T cells hindered optimal clearance of infection from tissues, In this report'cve analyze the flux of the V beta TCR repertoire in the lungs of C57BL/6 mice with reinfection histoplasmosis, We observed a significant increase in V beta6(+) T cells on days 7, 10, and 14, the peak and early resolution phases of infection. This skewing was preceded by an increased number of memory T cells within V beta6(+) cells. The VDJ sequences of V beta6 chains were oligoclonal during the early stages of the infection, suggesting that the expansion was driven by a small number of Ags, More than 96% of the expanded V beta6(+) cells were CD4(+). Depletion of V beta6(+) T cells but not V beta4(+) T cells induced a modest but significant delay in fungal clearance. Simultaneous depletion of V beta4(+) and V beta6(+) T cells induced a more pronounced impairment of host resistance. These studies illustrate the dynamic interactions between V beta families in the response to microbial challenge.