| Autor: |
Shah PD; 1Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland., Zhong Q; 1Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland., Lendermon EA; 2Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Pipeling MR; 2Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., McDyer JF; 2Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. |
| Jazyk: |
angličtina |
| Zdroj: |
Viral immunology [Viral Immunol] 2015 Jun; Vol. 28 (5), pp. 255-64. Date of Electronic Publication: 2015 May 18. |
| DOI: |
10.1089/vim.2015.0005 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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