comparison of human memory cd8 t cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue比较人类记忆的cd8 t细胞反应adenoviral早期和晚期蛋白质在外周血和淋巴组织.pdf

Comparison of Human Memory CD8 T Cell Responses to Adenoviral Early and Late Proteins in Peripheral Blood and Lymphoid Tissue 1 2 2 3 2 Amita Joshi , Biwei Zhao , Cara Romanowski , David Rosen , Phyllis Flomenberg * 1 Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America, 2 Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America, 3 Department of Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America Abstract Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-c and IL-2 but not perforin or TNF-a, whereas PB T cells were positive for IFN-c, TNF-a, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed t