Hyperexpansion of functional viral-specific CD8+ T cells in lymphopenia-associated MCMV pneumonitis

Pali D. Shah, Qiong Zhong, Elizabeth A. Lendermon, Matthew R. Pipeling, John F. McDyer

Research output: Contribution to journalArticlepeer-review

Abstract

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in immunocompromised hosts, many of whom undergo significant periods of lymphopenia. However, the impact of lymphopenia and subsequent immune reconstitution on T cell responses and pulmonary pathology are poorly understood. Using a model of primary murine CMV infection in mice treated with cyclophosphamide (CY), the relationship of CD8+ T cell reconstitution to pneumonitis pathology was studied. Female BALB/c mice were infected with murine CMV (MCMV) with/without CY on day 1 post-infection. Lung pathology and viral specific T cell responses were assessed on days 7-28. T cell lymphocyte subsets, effector responses, and MCMV specificity were assessed at baseline and after in vitro stimulation of cells with immediate-early peptide pp89. CY treatment of MCMV-infected mice resulted in interstitial pneumonitis not seen with MCMV alone. Compared to MCMV alone, on day 14, MCMV/CY mice had greater number of CD8+ T cells, a fourfold increase in absolute number of pp89 tetramer-specific CD8+ cells, and an eightfold increase in MCMV specific T cell effector responses (IFN-γ; p<0.001). This expansion was preceded by transient lymphopenia, increased viral titers, and, most strikingly, a 10-fold increased proliferative capacity in MCMV/CY mice. In the setting of CY-associated lymphopenia, concurrent MCMV infection alters immune reconstitution toward a hyperexpanded MCMV-specific CD8+ effector T cell pool that correlates with significant lung immunopathology.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalViral Immunology
Volume28
Issue number5
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology

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