Differential CMV-specific CD8+ effector T cell responses in the lung allograft predominate over the blood during human primary infection.

Published

Journal Article

Acquisition of T cell responses during primary CMV infection in lung transplant recipients (LTRs) appear critical for host defense and allograft durability, with increased mortality in donor+/recipient- (D+R-) individuals. In 15 D+R- LTRs studied, acute primary CMV infection was characterized by viremia in the presence or absence of pneumonitis, with viral loads higher in the lung airways/allograft compared with the blood. A striking influx of CD8+ T cells into the lung airways/allograft was observed, with inversion of the CD4+:CD8+ T cell ratio. De novo CMV-specific CD8+ effector frequencies in response to pooled peptides of pp65 were strikingly higher in lung mononuclear cells compared with the PBMC and predominated over IE1-specific responses and CD4+ effector responses in both compartments. The frequencies of pp65-specific cytokine responses were significantly higher in lung mononuclear cells compared with PBMC and demonstrated marked contraction with long-term persistence of effector memory CD8+ T cells in the lung airways following primary infection. CMV-tetramer+CD8+ T cells from PBMC were CD45RA- during viremia and transitioned to CD45RA+ following resolution. In contrast, CMV-specific CD8+ effectors in the lung airways/allograft maintained a CD45RA- phenotype during transition from acute into chronic infection. Together, these data reveal differential CMV-specific CD8+ effector frequencies, immunodominance, and polyfunctional cytokine responses predominating in the lung airways/allograft compared with the blood during acute primary infection. Moreover, we show intercompartmental phenotypic differences in CMV-specific memory responses during the transition to chronic infection.

Full Text

Duke Authors

Cited Authors

  • Pipeling, MR; West, EE; Osborne, CM; Whitlock, AB; Dropulic, LK; Willett, MH; Forman, M; Valsamakis, A; Orens, JB; Moller, DR; Lechtzin, N; Migueles, SA; Connors, M; McDyer, JF

Published Date

  • July 1, 2008

Published In

Volume / Issue

  • 181 / 1

Start / End Page

  • 546 - 556

PubMed ID

  • 18566421

Pubmed Central ID

  • 18566421

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.181.1.546

Language

  • eng

Conference Location

  • United States