V beta1+ J beta1.1+/V alpha2+ J alpha49+ CD4+ T cells mediate resistance against infection with Blastomyces dermatitidis.
Immunization with a cell wall/membrane (CW/M) and yeast cytosol extract (YCE) crude antigen from Blastomyces dermatitidis confers T-cell-mediated resistance against lethal experimental infection in mice. We isolated and characterized T cells that recognize components of these protective antigens and mediate protection. CD4+ T-cell clones elicited with CW/M antigen adoptively transferred protective immunity when they expressed a V alpha2+ J alpha49+/V beta1+ J beta1.1+ heterodimeric T-cell receptor (TCR) and produced high levels of gamma interferon (IFN-gamma). In contrast, V beta8.1/8.2+ CD4+ T-cell clones that were reactive against CW/M and YCE antigens and produced little or no IFN-gamma either failed to mediate protection or exacerbated the infection depending on the level of interleukin-5 expression. Thus, the outgrowth of protective T-cell clones against immunodominant antigens of B. dermatitidis is biased by a combination of the TCR repertoire and Th1 cytokine production.
Wüthrich
Marcel
M
Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospitals and Clinics, Madison, WI 53792, USA. mwuethri@wisc.edu
Filutowicz
Hanna I
HI
Allen
Holly L
HL
Deepe
George S
GS
Klein
Bruce S
BS
D019264:Adoptive Transfer; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001758:Blastomyces / Q000276:immunology*; D001759:Blastomycosis / Q000276:immunology / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002473:Cell Wall / Q000276:immunology; D002999:Clone Cells; D005434:Flow Cytometry; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D015003:Yeasts / Q000276:immunology
D000946:Antigens, Fungal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma