title: V beta 6+ and V beta 4+ T cells exert cooperative activity in clearance of secondary infection with Histoplasma capsulatum.
abstract: We previously studied the lung Vbeta TCR repertoire of C57BL/6 mice during primary infection with the pathogen Histoplasma capsulatum. We observed a consistent oligoclonal expansion of Vbeta4(+) T cells during the peak of infection and early stages of resolution. The Vbeta4(+) 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 we analyze the flux of the Vbeta TCR repertoire in the lungs of C57BL/6 mice with reinfection histoplasmosis. We observed a significant increase in Vbeta6(+) 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 Vbeta6(+) cells. The VDJ sequences of Vbeta6 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 Vbeta6(+) cells were CD4(+). Depletion of Vbeta6(+) T cells but not Vbeta4(+) T cells induced a modest but significant delay in fungal clearance. Simultaneous depletion of Vbeta4(+) and Vbeta6(+) T cells induced a more pronounced impairment of host resistance. These studies illustrate the dynamic interactions between Vbeta families in the response to microbial challenge.
authors.affiliation: Research Division, Veterans Administration Medical Center, Cincinnati, OH 45202, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Gomez
authors.forename: E O
authors.initials: EO
authors.lastname: Woodward
authors.forename: R
authors.initials: R
authors.lastname: Pilcher-Roberts
authors.forename: R S
authors.initials: RS
authors.lastname: Gibbons
authors.forename: G S
authors.initials: GS
authors.lastname: Deepe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006660:Histoplasmosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta