Lamousé-Smith E, McCarthy S A
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Cell Immunol. 1997 Aug 1;179(2):107-15. doi: 10.1006/cimm.1997.1162.
It has been demonstrated by several investigators that beta 2m-/- knockout mice are deficient in the expression of MHC Class I molecules but can nevertheless generate CD8(+) allospecific cytotoxic T cells following vigorous in vivo priming. We demonstrate here that in vivo priming is not necessary to generate MHC Class I allospecific CTL from beta 2m-/- mice. When splenocytes from naive unprimed beta 2m-/- mice were provided exogenous cytokines in MHC Class I disparate primary MLC, allospecific cytolytic effectors were generated. beta 2m-/- MHC Class I allospecific CTL that were CD3+ and Thy1.2+ were otherwise heterogeneous in phenotype, including CD8+, CD4+, CD8-CD4-, TCR alpha beta+, and TCR gamma delta+ T cells. This phenotypic variability of beta 2m-/- CTL generated in primary MLC reveals the diversity of CTL precursors that develop in vivo in the absence of MHC Class I.
多位研究者已证明,β2m-/-基因敲除小鼠的MHC I类分子表达存在缺陷,但在经过强烈的体内致敏后仍能产生CD8(+)同种异体特异性细胞毒性T细胞。我们在此证明,从β2m-/-小鼠产生MHC I类同种异体特异性CTL并不需要体内致敏。当在MHC I类不同的初次混合淋巴细胞培养中为未致敏的β2m-/-小鼠的脾细胞提供外源性细胞因子时,可产生同种异体特异性溶细胞效应细胞。β2m-/- MHC I类同种异体特异性CTL为CD3+和Thy1.2+,但其表型具有异质性,包括CD8+、CD4+、CD8-CD4-、TCR αβ+和TCR γδ+ T细胞。在初次混合淋巴细胞培养中产生的β2m-/- CTL的这种表型变异性揭示了在没有MHC I类的情况下在体内发育的CTL前体的多样性。