CD4+ and CD8+ T cells exhibit differential requirements for CCR7-mediated antigen transport during influenza infection.
Upon encounter of viral Ags in an inflammatory environment, dendritic cells up-regulate costimulatory molecules and the chemokine receptor CCR7, with the latter being pivotal for their migration to the lymph node. By utilizing mice deficient in CCR7, we have examined the requirement of dendritic cell-mediated Ag transport from the lung to the draining lymph node for the induction of anti-influenza immune responses in vivo. We found that CCR7-mediated migration of dendritic cells was more crucial for CD8(+) T cell than CD4(+) T cell responses. While no specific CD8(+) T cell response could be detected in the airways or lymphoid tissues during the primary infection, prolonged infection in CCR7-deficient mice did result in a sustained inflammatory chemokine profile, which led to nonspecific CD8(+) T cell recruitment to the airways. The recruitment of influenza-specific CD4(+) T cells to the airways was also below levels of detection in the absence of CCR7 signaling, although a small influenza-specific CD4(+) T cell population was detectable in the draining lymph node, which was sufficient for the generation of class-switched anti-influenza Abs and a normal CD4(+) T cell memory population. Overall, our data show that CCR7-mediated active Ag transport is differentially required for CD4(+) and CD8(+) T cell expansion during influenza infection.
Heer
Alex K
AK
Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology, Zurich-Schlieren, Switzerland.
Harris
Nicola L
NL
Kopf
Manfred
M
Marsland
Benjamin J
BJ
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D054400:Receptors, CCR7 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000914:Antibodies, Viral; D000956:Antigens, Viral; C515371:Ccr7 protein, mouse; D018925:Chemokines; D012333:RNA, Messenger; D054400:Receptors, CCR7