Institut National de la Recherche Agronomique, Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
PLoS One. 2013;8(4):e60175. doi: 10.1371/journal.pone.0060175. Epub 2013 Apr 2.
Teleost fish express highly diverse naive TCRβ (TRB) repertoires and mount strong public and private clonal responses upon infection with pathogens. Fish T cells express typical markers such as CD8, CD4-1 and CD4-2, CD3, CD28 and CTLA4. Fish CD8(+) T cells have been shown to be responsible for antigen-specific cell-mediated cytotoxicity in in vitro systems using histo-compatible effector and target cells. We compare here the complexity of TRB repertoires between FACS sorted CD8(+) and CD8(-) T cells from spleen and pronephros of rainbow trout. In contrast to human, while the TRB repertoire is highly diverse and polyclonal in CD8(+) T cells of naïve fish, it appeared very different in CD8(-) lymphocytes with irregular CDR3 length distributions suggesting a dominance of activated clones already in naïve fish or the presence of non conventional T cells. After infection with a systemic virus, CD8(+) T cells mount a typical response with significant skewing of CDR3 length profiles. The infection also induces significant modifications of the TRB repertoire expressed by the CD8(-) fraction, but for a different set of V/J combinations. In this fraction, the antiviral response results in an increase of the peak diversity of spectratypes. This unusual observation reflects the presence of a number of T cell expansions that rise the relative importance of minor peaks of the highly skewed distributions observed in unchallenged animals. These results suggest that the diversity of TRB expressed by CD8(+) and CD8(-) αβ T cells may be subjected to different regulatory patterns in fish and in mammals.
硬骨鱼类表达高度多样化的初始 TCRβ(TRB)库,并在感染病原体后产生强烈的公共和私人克隆反应。鱼类 T 细胞表达典型的标志物,如 CD8、CD4-1 和 CD4-2、CD3、CD28 和 CTLA4。鱼类 CD8(+) T 细胞已被证明在使用组织相容性效应器和靶细胞的体外系统中负责抗原特异性细胞介导的细胞毒性。我们在这里比较了虹鳟鱼脾脏和前肾中 FACS 分选的 CD8(+)和 CD8(-) T 细胞之间的 TRB 库复杂性。与人类不同,虽然在幼稚鱼类的 CD8(+) T 细胞中,TRB 库具有高度多样性和多克隆性,但在 CD8(-)淋巴细胞中,CDR3 长度分布不规则,表明激活克隆已经在幼稚鱼类中占主导地位,或者存在非传统 T 细胞。感染系统性病毒后,CD8(+) T 细胞会产生典型反应,CDR3 长度谱显著倾斜。感染还会诱导 CD8(-) 细胞表达的 TRB 库发生显著变化,但 V/J 组合不同。在该亚群中,抗病毒反应会增加谱型的多样性峰值。这种异常观察反映了存在大量 T 细胞扩增,这些扩增增加了在未受挑战的动物中观察到的高度倾斜分布的次要峰的相对重要性。这些结果表明,CD8(+)和 CD8(-)αβ T 细胞表达的 TRB 多样性可能受到鱼类和哺乳动物中不同调节模式的影响。