Rosenberg A S, Sechler J M, Horvath J A, Maniero T G, Bloom E T
Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Eur J Immunol. 1994 Jun;24(6):1312-6. doi: 10.1002/eji.1830240611.
The present investigation explored age-related alterations in T cell populations mediating allospecific responses in vivo. Healthy aged and young H-2b and H-2bxH-2k mice were engrafted with major histocompatibility complex (MHC) class II-disparate bm12 skin, rejection of which requires CD8+ T cells, and MHC class I-disparate bm1 skin, rejection of which requires CD8+ T cells. Aged mice of both genders exhibited prolonged survival of bm12 skin grafts relative to their young counterparts but rejected bm1 skin grafts at a rate equivalent to that of young mice. Consistent with prolonged survival of bm12 skin grafts, markedly diminished levels of Iabm12 CTL activity were elicited from T cells of aged mice in vitro. However, no such decline was observed in the level of Kbm1 CTL from T cells of aged mice. The alterations in Iabm12 allospecific responses were not attributable to quantitative changes in CD4+ T cells of aged mice, and addition of soluble T cell helper factors to response cultures of aged mice did not augment Iabm12 cytotoxic T lymphocytes activity. These data demonstrate that aging fundamentally affects CD4+ T cell-mediated allospecific responses particularly in vivo, and that deficient generation of soluble T cell helper factors alone cannot explain this deficit.
本研究探讨了体内介导同种异体特异性反应的T细胞群体与年龄相关的变化。将主要组织相容性复合体（MHC）II类不相容的bm12皮肤移植到健康的老年和年轻H-2b及H-2bxH-2k小鼠体内，其排斥反应需要CD8+T细胞；同时将MHC I类不相容的bm1皮肤移植到这些小鼠体内，其排斥反应需要CD4+T细胞。相对于年轻小鼠，老年雌雄小鼠的bm12皮肤移植存活时间延长，但排斥bm1皮肤移植的速度与年轻小鼠相当。与bm12皮肤移植存活时间延长一致，老年小鼠T细胞在体外诱导产生的Iabm12细胞毒性T淋巴细胞（CTL）活性水平显著降低。然而，老年小鼠T细胞的Kbm1 CTL水平未观察到此类下降。Iabm12同种异体特异性反应的变化并非归因于老年小鼠CD4+T细胞的数量变化，并且向老年小鼠的反应培养物中添加可溶性T细胞辅助因子并未增强Iabm12细胞毒性T淋巴细胞的活性。这些数据表明，衰老从根本上影响CD4+T细胞介导的同种异体特异性反应，尤其是在体内，并且仅可溶性T细胞辅助因子生成不足无法解释这种缺陷。
