Hwang Melissa L, Lukens John R, Bullock Timothy N J
Department of Pathology, Human Immune Therapy Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
J Immunol. 2007 Nov 1;179(9):5829-38. doi: 10.4049/jimmunol.179.9.5829.
CD4(+) T cells are known to provide support for the activation and expansion of primary CD8(+) T cells, their subsequent differentiation, and ultimately their survival as memory cells. However, the importance of cognate memory CD4(+) T cells in the expansion of memory CD8(+) T cells after re-exposure to Ag has been not been examined in detail. Using bone marrow-derived dendritic cells pulsed with cognate or noncognate MHC class I- and class II-restricted peptides, we examined whether the presence of memory CD4(+) T cells with the same Ag specificity as memory CD8(+) T cells influenced the quantity and quality of the secondary CD8(+) T cell response. After recombinant vaccinia virus-mediated challenge, we demonstrate that, although cognate memory CD4(+) T cells are not required for activation of secondary CD8(+) T cells, their presence enhances the expansion of cognate memory CD8(+) T cells. Cognate CD4(+) T cell help results in an approximate 2-fold increase in the frequency of secondary CD8(+) T cells in secondary lymphoid tissues, and can be accounted for by enhanced proliferation in the secondary CD8(+) T cell population. In addition, cognate memory CD4(+) T cells further selectively enhance secondary CD8(+) T cell infiltration of tumor-associated peripheral tissue, and this is accompanied by increased differentiation into effector phenotype within the secondary CD8(+) T cell population. The consequence of these improvements to the magnitude and phenotype of the secondary CD8(+) T cell response is substantial increase in control of tumor outgrowth.
已知CD4(+) T细胞可支持初始CD8(+) T细胞的激活和扩增、其随后的分化以及最终作为记忆细胞的存活。然而，同源记忆CD4(+) T细胞在再次接触抗原后对记忆CD8(+) T细胞扩增中的重要性尚未得到详细研究。我们使用用同源或非同源MHC I类和II类限制性肽脉冲处理的骨髓来源的树突状细胞，研究了与记忆CD8(+) T细胞具有相同抗原特异性的记忆CD4(+) T细胞的存在是否会影响次级CD8(+) T细胞反应的数量和质量。在重组痘苗病毒介导的攻击后，我们证明，虽然同源记忆CD4(+) T细胞对于次级CD8(+) T细胞的激活不是必需的，但它们的存在会增强同源记忆CD8(+) T细胞的扩增。同源CD4(+) T细胞的辅助导致次级淋巴组织中次级CD8(+) T细胞频率增加约2倍，这可以通过次级CD8(+) T细胞群体中增殖增强来解释。此外，同源记忆CD4(+) T细胞进一步选择性增强肿瘤相关外周组织的次级CD8(+) T细胞浸润，并且这伴随着次级CD8(+) T细胞群体中效应表型分化增加。次级CD8(+) T细胞反应的幅度和表型的这些改善的结果是对肿瘤生长控制的显著增加。
