Wüthrich Marcel, Filutowicz Hanna I, Allen Holly L, Deepe George S, Klein Bruce S
Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospitals and Clinics, Madison, WI 53792, USA.
Infect Immun. 2007 Jan;75(1):193-200. doi: 10.1128/IAI.01148-06. Epub 2006 Oct 9.
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.
用皮炎芽生菌的细胞壁/细胞膜(CW/M)和酵母胞质溶胶提取物(YCE)粗抗原进行免疫接种可赋予小鼠T细胞介导的针对致死性实验性感染的抵抗力。我们分离并鉴定了识别这些保护性抗原成分并介导保护作用的T细胞。当用CW/M抗原诱导产生的CD4 + T细胞克隆表达Vα2 + Jα49 + / Vβ1 + Jβ1.1 +异二聚体T细胞受体(TCR)并产生高水平的γ干扰素(IFN-γ)时,可通过过继转移赋予保护性免疫。相比之下,对CW/M和YCE抗原具有反应性且几乎不产生或不产生IFN-γ的Vβ8.1/8.2 + CD4 + T细胞克隆,根据白细胞介素-5的表达水平,要么无法介导保护作用,要么会加重感染。因此,针对皮炎芽生菌免疫显性抗原的保护性T细胞克隆的生长受到TCR库和Th1细胞因子产生的共同影响。