CC chemokine receptor 7 expression by effector/memory CD4+ T cells depends on antigen specificity and tissue localization during influenza A virus infection.
The lung is an important entry site for respiratory pathogens such as influenza A virus. In order to combat such invading infectious agents, effector/memory T cells home to the lung and other peripheral tissues as well as lymphoid organs. In this process, chemokines and their receptors fulfill important roles in the guidance of T cells into such organs and specialized microenvironments within tissues. In this study, we determined if CD4(+) T cells residing in different lung compartments and draining lymph nodes of influenza A virus-infected and naïve mice express receptors allowing their recirculation into secondary lymphoid tissues. We found high levels of l-selectin and CC chemokine receptor 7 (CCR7) expression in lung-derived CD4(+) T cells, similar to that detected on T cells in secondary lymphoid organs. Upon influenza A virus infection, the bulk of gamma interferon-positive (IFN-gamma(+)) and IFN-gamma(-) CD4(+) T cells recovered from lung parenchyma retained functional CCR7, whereas virus-specific IFN-gamma-producing T cells were CCR7(-). In contrast, a majority of virus-specific IFN-gamma(+) T cells in the lung draining lymph node were CCR7(+). Independent of infection, CD4(+) T cells obtained from the lung airways exhibited the lowest expression level of l-selectin and CCR7, indicating that T cells at this anatomical site represent the most differentiated effector cell type, lacking the ability to recirculate. Our results suggest that effector/memory T cells that enter inflammatory sites retain functional CCR7 expression, which is lost only upon response to viral antigen and after localization to the final effector site.
Debes
Gudrun F
GF
Experomentelle Rheumatologie Medizinische Klinik, Charité, Humboldt Universität,, Germany. debes@stanford.edu
Bonhagen
Kerstin
K
Wolff
Thorsten
T
Kretschmer
Ute
U
Krautwald
Stefan
S
Kamradt
Thomas
T
Hamann
Alf
A
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D009928:Organ Specificity; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
D000956:Antigens, Viral; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin; D007371:Interferon-gamma