The role of antigen in the localization of naive, acutely activated, and memory CD8(+) T cells to the lung during influenza pneumonia.
The role of Ag in the recruitment and localization of naive, acutely activated, and memory CD8(+) T cells to the lung during influenza infection was explored using TCR-transgenic (Tg) mice. Naive, Thy1.2(+)CD8(+) OT-I TCR-Tg cells were primed and recruited to the lung after transfer into congenic Thy1.1(+) recipients challenged with a genetically engineered influenza virus (influenza A/WSN/33 (WSN)-OVA(I)) containing the K(b) restricted OVA(257-264) epitope (siinfekl) in the viral neuraminidase stalk. However, if the transferred animals were infected with a similar influenza virus that expressed an irrelevant K(b) epitope (WSN-PEPII), no TCR-Tg T cells were detectable in the lung, although they were easily visible in the lymphoid organs. Conversely, there were substantial numbers of OT-I cells found in the lungs of WSN-PEPII-infected mice when the animals had been previously, or were concurrently, infected with a recombinant vaccinia virus expressing OVA. Similar results were obtained with nontransgenic populations of memory CD8(+) T cells reactive to a murine gamma-herpesvirus-68 Ag. Interestingly, the primary host response to the immunodominant influenza nucleoprotein epitope was not affected by the presence of memory or recently activated OT-I T cells. Thus, although Ag is required to activate the T cells, the subsequent localization of T cells to the lung during a virus infection is a property of recently activated and memory T cells and is not necessarily driven by Ag in the lung.
Topham
D J
DJ
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642, USA. david_topham@urmc.rochester.edu
Castrucci
M R
MR
Wingo
F S
FS
Belz
G T
GT
Doherty
P C
PC
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D004274:DNA, Recombinant / Q000008:administration & dosage; D004279:DNA, Viral / Q000235:genetics; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D019672:Genes, T-Cell Receptor; D007156:Immunologic Memory; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D011024:Pneumonia, Viral / Q000276:immunology*; D018144:Rhadinovirus / Q000276:immunology
D000956:Antigens, Viral; D004274:DNA, Recombinant; D004279:DNA, Viral; D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin