CD8+ T cells clear influenza virus by perforin or Fas-dependent processes.
Influenza virus infection is controlled in CD4-depleted mice that are also defective for the expression of either Fas (Fas-/-) or perforin (P-/-). Virus-immune P+/+ and P-/- CD8+ T cells can thus function in, respectively, a Fas-/- or Fas+/+ lung environment. The obvious question is whether the P-/- CD8+ set is effective in Fas-/- mice, a conclusion that would tend to favor cytokine secretion as the mode of virus clearance. Short term chimeras were made with P-/- bone marrow, P+/+ or P-/- T cells, and Fas+/+ or Fas-/- irradiated recipients. While the P+/+ CD8+ population cleared the virus from Fas+/+ and Fas-/- respiratory epithelium, the P-/- effectors were operational only if there was the potential for Fas to be expressed on radiation-resistant lung cells. Target cell destruction mediated via the Fas or perforin pathways is clearly the primary mechanism used by CD8+ T cells to terminate this viral pneumonia.
Topham
D J
DJ
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Tripp
R A
RA
Doherty
P C
PC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009976:Orthomyxoviridae Infections / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011828:Radiation Chimera; D019014:fas Receptor / Q000494:pharmacology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin