Lisa Jacobson

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

Matthew R Pipeling; Erin E West; Christine M Osborne; Amanda B Whitlock; Lesia K Dropulic; Matthew H Willett; Michael Forman; Alexandra Valsamakis; Jonathan B Orens; David R Moller; et al. (Profiled Authors: John Mcdyer; Jonathan Orens; David Moller; Noah Lechtzin; Alexandra Valsamakis)

Division of Pulmonary and Critical Care Medicine, Department of Pathology and Medical Microbiology, Johns Hopkins University, School of Medicine, Baltimore, MD 21224, USA.
Journal of immunology (Baltimore, Md. : 1950) 2008;181(1):546-56.

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.

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