Comparison of human memory CD8 T cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue.

Authors

Amita Joshi, Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Biwei Zhao, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania
Cara Romanowski, Department of Medicine, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
David Rosen, Department of Otolaryngology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Phyllis Flomenberg, Department of Medicine, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

5-1-2011

Comments

This article has been peer reviewed and is published in PLoS One 2011, 6(5). The published version is available at DOI: 10.1371/journal.pone.0020068. © Public Library of Science

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-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, 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 targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16-24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients.

Recommended Citation

Joshi, Amita; Zhao, Biwei; Romanowski, Cara; Rosen, David; and Flomenberg, Phyllis, "Comparison of human memory CD8 T cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue." (2011). Department of Microbiology and Immunology Faculty Papers. Paper 23.
https://jdc.jefferson.edu/mifp/23

PubMed ID

21637763