title: Differentiation-dependent differences in murine T cell susceptibility to negative regulation by the lung.
abstract: A large number of viral infections are contracted via the respiratory route. Thus, an effective immune response at this site is of vital importance. Past studies in murine models analyzing a number of viruses have reported that CD8(+) effector T cells entering the lung after respiratory infection exhibit significant functional inactivation. The impaired function in these cells has been proposed to be the result of infection-induced changes in the lung; however, we have found that loss of function can occur in effector CD8(+) T cells present in the lung, even in the absence of infection. This functional inactivation takes place within 48 hours of entry into the lung, and is seen only in effector cells residing in the lung parenchyma, and not the airway. In this study, we have extended our findings to show that functional impairment of these effector cells is not initiated by bone marrow-derived cells, and is independent of proliferation in the lung tissue. Of critical importance, we have also determined that the susceptibility to functional inactivation is a common property shared by most effector cells. Finally, we show that the susceptibility to loss of function is actively regulated throughout differentiation. Although naive CD8(+) T cells, like effector cells, are negatively regulated as a result of residence in the lung, memory cells exhibit profound resistance to functional inactivation. The selective resistance of CD8(+) memory cells may allow the host to limit damage during the effector phase while retaining a protective response that can effectively limit subsequent infection.
authors.affiliation: Department of Microbiology & Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Rhea Y
authors.initials: RY
authors.lastname: Busick
authors.forename: Rama D
authors.initials: RD
authors.lastname: Yammani
authors.forename: Martha A
authors.initials: MA
authors.lastname: Alexander-Miller
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006388:Hemagglutinins / Q000378:metabolism; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006388:Hemagglutinins; D007371:Interferon-gamma