Cellular mechanisms involved in protection against influenza virus infection in transgenic mice expressing a TCR receptor specific for class II hemagglutinin peptide in …

A Bot, S Casares, S Bot, H von Boehmer… - The Journal of …, 1998 - journals.aai.org
A Bot, S Casares, S Bot, H von Boehmer, C Bona
The Journal of Immunology, 1998journals.aai.org
Mice transgenic for a TCR that recognizes peptide 110–120 of hemagglutinin of PR8
influenza virus in the context of MHC class II IE d molecules express the transgenes in both
CD4+ and CD8+ T cells. We have found that these TCR-hemagglutinin (TCR-HA) transgenic
mice display a significantly increased resistance to the primary infection with PR8 virus
compared with the wild-type mice. The TCR-HA transgenic mice mounted significant MHC
type II and enhanced MHC type I-restricted cytotoxicity as well as increased cytokine …
Abstract
Mice transgenic for a TCR that recognizes peptide 110–120 of hemagglutinin of PR8 influenza virus in the context of MHC class II IE d molecules express the transgenes in both CD4+ and CD8+ T cells. We have found that these TCR-hemagglutinin (TCR-HA) transgenic mice display a significantly increased resistance to the primary infection with PR8 virus compared with the wild-type mice. The TCR-HA transgenic mice mounted significant MHC type II and enhanced MHC type I-restricted cytotoxicity as well as increased cytokine responses in both spleen and lungs after infection with PR8 virus. In contrast, the primary humoral response against PR8 virus was not significantly different from that of the wild-type mice. In vivo depletion and adoptive cell transfer experiments demonstrated that both CD4+ and CD8+ TCR-HA+ T cell subsets were required for the complete clearance of pulmonary virus following infection with a dose that is 100% lethal in wild-type mice. Whereas CD4+ TCR-HA+ T cells were necessary for effective activation and local recruitment of CD8+ T cells, CD8+ TCR-HA+ T cells showed a Th1-biased pattern and MHC type II-restricted cytotoxicity. However, in the absence of in vivo expression of MHC type I molecules on the infected cells, the protection conferred by the TCR-HA+ T cells was impaired, indicating that the enhanced MHC class I-restricted cytotoxicity due to TCR-HA+ CD4+ Th cells was a critical element for clearance of the pulmonary virus by the transgenic mice.
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