Pathogen-related differences in the abundance of presented antigen are reflected in CD4+ T cell dynamic behavior and effector function in the lung.
Publication/Presentation Date
2-15-2014
Abstract
Exposure to pathogens in the periphery elicits effector T cell differentiation in local lymph nodes followed by migration of activated T cells to and within the infected site. However, the relationships among pathogen abundance, Ag display on MHC molecules, effector T cell dynamics, and functional responses at the infected sites are incompletely characterized. In this study, we compared CD4(+) T cell effector dynamics and responses during pulmonary mycobacterial infection versus acute influenza infection. Two-photon imaging together with in situ as well as ex vivo analysis of cytokine production revealed that the proportion of migration-arrested, cytokine-producing effector T cells was dramatically higher in the influenza-infected lungs due to substantial differences in Ag abundance in the two infectious states. Despite the marked inflammatory conditions associated with influenza infection, histocytometric analysis showed that cytokine production was focal, with a restriction to areas of significant Ag burden. Optimal effector function is thus constrained by the availability of TCR ligands, pointing to the value of increasing Ag stimulation rather than effector numbers in harnessing CD4(+) T cells for therapeutic purposes in such conditions.
Volume
192
Issue
4
First Page
1651
Last Page
1660
ISSN
1550-6606
Published In/Presented At
Torabi-Parizi, P., Vrisekoop, N., Kastenmuller, W., Gerner, M. Y., Egen, J. G., & Germain, R. N. (2014). Pathogen-related differences in the abundance of presented antigen are reflected in CD4+ T cell dynamic behavior and effector function in the lung. Journal of immunology (Baltimore, Md. : 1950), 192(4), 1651–1660. https://doi.org/10.4049/jimmunol.1301743
Disciplines
Medicine and Health Sciences
PubMedID
24431231
Department(s)
Department of Medicine
Document Type
Article