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Localization of Viral Epitope-Specific CD8 T Cells during Cytomegalovirus Latency in the Lungs and Recruitment to Lung Parenchyma by Airway Challenge Infection
| Content Provider | MDPI |
|---|---|
| Author | Blaum, Franziska Lukas, Dominika Reddehase, Matthias J. Lemmermann, Niels A. W. |
| Copyright Year | 2021 |
| Description | Interstitial pneumonia is a life-threatening clinical manifestation of cytomegalovirus infection in recipients of hematopoietic cell transplantation (HCT). The mouse model of experimental HCT and infection with murine cytomegalovirus revealed that reconstitution of virus-specific $CD8^{+}$ T cells is critical for resolving productive lung infection. $CD8^{+}$ T-cell infiltrates persisted in the lungs after the establishment of latent infection. A subset defined by the phenotype $KLRG1^{+}CD62L^{−}$ expanded over time, a phenomenon known as memory inflation (MI). Here we studied the localization of these inflationary T effector-memory cells (iTEM) by comparing their frequencies in the intravascular and transmigration compartments, the IVC and TMC, respectively, with their frequency in the extravascular compartment (EVC), the alveolar epithelium. Frequencies of viral epitope-specific iTEM were comparable in the IVC and TMC but were reduced in the EVC, corresponding to an increase in $KLRG1^{−}CD62L^{−}$ conventional T effector-memory cells (cTEM) and a decrease in functional $IFNγ^{+}CD8^{+}$ T cells. As maintained expression of KLRG1 requires stimulation by antigen, we conclude that iTEM lose KLRG1 and convert to cTEM after transmigration into the EVC because pneumocytes are not latently infected and, therefore, do not express antigens. Accordingly, antigen re-expression upon airway challenge infection recruited virus-specific $CD8^{+}$ T cells to TMC and EVC. |
| Starting Page | 918 |
| e-ISSN | 20751729 |
| DOI | 10.3390/life11090918 |
| Journal | Life |
| Issue Number | 9 |
| Volume Number | 11 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-09-04 |
| Access Restriction | Open |
| Subject Keyword | Life Immunology Antigen Presentation Cd8 T Cells Cytomegalovirus (cmv) Effector-memory T Cells (tem) Hematopoietic Cell Transplantation (hct) Interstitial Pneumonia Latent Infection Lungs Lung Parenchyma Memory Inflation (mi) |
| Content Type | Text |
| Resource Type | Article |