Differential CMV-Specific CD8 super(+) Effector T Cell Responses in the Lung Allograft Predominate over the Blood during Human Primary Infection

• Published in: The Journal of immunology (1950) Vol. 181; no. 1; pp. 546 - 556
• Main Authors: Pipeling, Matthew R, West, Erin E, Osborne, Christine M, Whitlock, Amanda B, Dropulic, Lesia K, Willett, Matthew H, man, Michael, Valsamakis, Alexandra, Orens, Jonathan B, Moller, David R, Lechtzin, Noah, Migueles, Stephen A, Connors, Mark, McDyer, John F
• Format: Journal Article
• Language: English
• Published: 01.07.2008
• Subjects: Cytomegalovirus
• ISSN: 0022-1767; 1550-6606

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 super(+)/recipient super(-) (D super(+)R super(-)) individuals. In 15 D super(+)R super(-) 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 super(+) T cells into the lung airways/allograft was observed, with inversion of the CD4 super(+):CD8 super(+) T cell ratio. De novo CMV-specific CD8 super(+) 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 super(+) 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 super(+) T cells in the lung airways following primary infection. CMV-tetramer super(+)CD8 super(+) T cells from PBMC were CD45RA super(-) during viremia and transitioned to CD45RA super(+) following resolution. In contrast, CMV-specific CD8 super(+) effectors in the lung airways/allograft maintained a CD45RA super(-) phenotype during transition from acute into chronic infection. Together, these data reveal differential CMV-specific CD8 super(+) 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.