Visualization and characterization of respiratory syncytial virus F-specific CD8(+) T cells during experimental virus infection.
CTL play a major role in the clearance of respiratory syncytial virus (RSV) during experimental pulmonary infection. The fusion (F) glycoprotein of RSV is a protective Ag that elicits CTL and Ab response against RSV infection in BALB/c mice. We used the strategy of screening a panel of overlapping synthetic peptides corresponding to the RSV F protein and identified an immunodominant H-2K(d)-restricted epitope (F(85-93); KYKNAVTEL) recognized by CD8(+) T cells from BALB/c mice. We enumerated the F-specific CD8(+) T cell response in the lungs of infected mice by flow cytometry using tetramer staining and intracellular cytokine synthesis. During primary infection, F(85-93)-specific effector CD8(+) T cells constitute approximately 4.8% of pulmonary CD8(+) T cells at the peak of the primary response (day 8), whereas matrix 2-specific CD8(+) T cells constituted approximately 50% of the responding CD8(+) T cell population in the lungs. When RSV F-immune mice undergo a challenge RSV infection, the F-specific CD8(+) T cell response is accelerated and dominates, whereas the primary response to the matrix 2 epitope in the lungs is reduced by approximately 20-fold. In addition, we found that activated F-specific effector CD8(+) T cells isolated from the lungs of RSV-infected mice exhibited a lower than expected frequency of IFN-gamma-producing CD8(+) T cells and were significantly impaired in ex vivo cytolytic activity compared with competent F-specific effector CD8(+) T cells generated in vitro. The significance of these results for the regulation of the CD8(+) T cell response to RSV is discussed.
Chang
J
J
Beirne B. Carter Center for Immunology Research and Department of Pathology and Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Srikiatkhachorn
A
A
Braciale
T J
TJ
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D014764:Viral Proteins