Journal article
The pulmonary localization of virus-specific T lymphocytes is governed by the tissue tropism of infection
Journal of virology, Vol.88(16), pp.9010-9016
08/2014
DOI: 10.1128/JVI.00329-14
PMCID: PMC4136240
PMID: 24899187
Abstract
The migration of pathogen-specific T cells into nonlymphoid tissues, such as the lung, is critical to control peripheral infections. Use of in vivo intravascular labeling of leukocytes has allowed for improved discrimination between cells located in the blood from cells present within peripheral tissues, such as the lung. This is particularly important in the lung, which is comprised of an intricate network of blood vessels that harbors a large proportion of the total blood volume at any given time. Recent work has demonstrated that >80% of antigen-specific effector CD8 T cells remain in the pulmonary vasculature following an intratracheal infection with a systemic viral pathogen. However, it remains unclear what proportion of effector CD8 T cells are located within lung tissue following a localized respiratory viral infection. We confirm that most effector and memory CD8 T cells are found in the vasculature after an intranasal infection with the systemic pathogens lymphocytic choriomeningitis virus (LCMV) or vaccinia virus (VACV). In contrast, following pulmonary viral infections with either respiratory syncytial virus (RSV) or influenza A virus (IAV), 80 to 90% of the antigen-specific effector CD8 T cells were located within lung tissue. Similarly, the majority of antigen-specific CD4 T cells were present within lung tissue during a pulmonary viral infection. Furthermore, a greater proportion of gamma interferon-positive (IFN-γ(+)) effector CD8 and CD4 T cells were located within lung tissue following a localized respiratory viral infection. Our results indicate that T cells exhibit significantly altered distribution patterns dependent upon the tissue tropism of the infection.
The migration of T cells to nonlymphoid sites, such as the lung, is critical to mediate clearance of viral infections. The highly vascularized lung holds up to 40% of blood, and thus, the T cell response may be a reflection of lymphocytes localized to the pulmonary vasculature instead of lung tissue. We examined the localization of T cell responses within the lung following either a localized or systemic viral infection. We demonstrate that following intranasal infection with a systemic pathogen, most T cells are localized to the pulmonary vasculature. In contrast, T cells are primarily localized to lung tissue following a respiratory viral infection. Our results demonstrate vast differences in the localization of T cell responses within the lung parenchyma between pathogens that can replicate locally versus systemically and that intravascular antibody labeling can be utilized to assess the localization patterns of T cell responses in nonlymphoid organs.
Details
- Title: Subtitle
- The pulmonary localization of virus-specific T lymphocytes is governed by the tissue tropism of infection
- Creators
- Cory J Knudson - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USAKayla A Weiss - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USAStacey M Hartwig - Department of Microbiology, University of Iowa, Iowa City, Iowa, USASteven M Varga - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA Department of Microbiology, University of Iowa, Iowa City, Iowa, USA Department of Pathology, University of Iowa, Iowa City, Iowa, USA steven-varga@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.88(16), pp.9010-9016
- DOI
- 10.1128/JVI.00329-14
- PMID
- 24899187
- PMCID
- PMC4136240
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R56AI106776 / NIAID NIH HHS T32AI007485 / NIAID NIH HHS R56 AI106776 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS
- Language
- English
- Date published
- 08/2014
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology
- Record Identifier
- 9984083881302771
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