Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus-infected epithelium.
Minimal numbers of CD8+ T cells are found in bronchoalveolar lavage (BAL) populations recovered from Sendai virus-infected mice that are homozygous (-/-) for a beta 2-microglobulin (beta 2-m) gene disruption. The prevalence of the CD8+ set was substantially increased in the pneumonic lungs of 8-12-week radiation chimeras made using substantially class I major histocompatibility complex (MHC) glycoprotein-negative beta 2-m (-/-) recipients and normal beta 2-m (+/+) bone marrow. Even so, the CD8+ (but not the CD4+) lymphocyte counts were still much lower than in the (+/+)-->(+/+) controls. The (+/+)-->(+/+) and (+/+)-->(-/-) chimeras cleared Sendai virus and potent virus-immune CD8+ cytotoxic T lymphocytes (CTL) specific for H-2Kb+viral nucleoprotein peptide were found in the BAL from both groups. However, following in vivo depletion of the CD4+ population, only the (+/+)-->(+/+) mice were able to deal with the infection. Similarly, adoptively transferred, H-2Kb-restricted CD8+ T cells from previously-primed (+/+) mice also failed to clear virus from the lungs of (+/+)-->(-/-) chimeras infected within 2 weeks of reconstitution with bone marrow, though they were effective in the (+/+)-->(+/+) controls. Sendai virus-immune CD8+ T cells are thus unable to eliminate virus-infected beta 2-m (-/-) lung epithelial cells that might be thought to be expressing very small amounts of either isolated class I heavy chain, or class I MHC glycoprotein that has bound beta 2-m derived from beta 2-m (+/+) T cells or macrophages present in the pneumonic lung. Furthermore, the CD8+ CTL that are being exposed to beta 2-m (+/+) stimulators in the BAL population cannot operate in some bystander mode to clear virus from respiratory epithelium.
Hou
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Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Doherty
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PC
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003601:Cytotoxicity Tests, Immunologic; D004848:Epithelium / Q000276:immunology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000235:genetics; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology* / Q000628:therapy; D011828:Radiation Chimera / Q000276:immunology; D012137:Respiratory System / Q000276:immunology* / Q000821:virology
D006183:H-2 Antigens