CD8(+) T cell-mediated injury in vivo progresses in the absence of effector T cells.
Tissue injury is a common sequela of acute virus infection localized to a specific organ such as the lung. Tissue injury is an immediate consequence of infection with lytic viruses. It can also result from the direct destruction of infected cells by effector CD8(+) T lymphocytes and indirectly through the action of the T cell-derived proinflammatory cytokines and recruited inflammatory cells on infected and uninfected tissue. We have examined CD8(+) T cell-mediated pulmonary injury in a transgenic model in which adoptively transferred, virus-specific cytotoxic T lymphocytes (CTLs) produce lethal, progressive pulmonary injury in recipient mice expressing the viral target transgene exclusively in the lungs. We have found that over the 4-5 day course of the development of lethal pulmonary injury, the effector CTLs, while necessary for the induction of injury, are present only transiently (24-48 h) in the lung. We provide evidence that the target of the antiviral CD8(+) T cells, the transgene expressing type II alveolar cells, are not immediately destroyed by the effector T cells. Rather, after T cell-target interaction, the type II alveolar cells are stimulated to produce the chemokine monocyte chemoattractant protein 1. These results reinforce the concept that, in vivo, the cellular targets of specific CTLs may participate directly in the development of progressive tissue injury by activating in response to interaction with the T cells and producing proinflammatory mediators without sustained in vivo activation of CD8(+) T cell effectors.
Small
B A
BA
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Dressel
S A
SA
Lawrence
C W
CW
Drake
D R
DR
Stoler
M H
MH
Enelow
R I
RI
Braciale
T J
TJ
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018932:Chemokine CCL2 / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006389:Hemagglutinins, Viral / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D018932:Chemokine CCL2; D006389:Hemagglutinins, Viral