Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus.
Hantavirus cardiopulmonary syndrome is a zoonotic illness associated with a systemic inflammatory immune response, capillary leak, noncardiogenic pulmonary edema, and shock in humans. Cytokines, including TNF, IFN-gamma, and lymphotoxin, are thought to contribute to its pathogenesis. In contrast, infected rodent reservoirs of hantaviruses experience few or no pathologic changes and the host rodent can remain persistently infected for life. Generally, it is unknown why such dichotomous immune responses occur between humans and reservoir hosts. Thus, we examined CD4(+) T cell responses from one such reservoir, the deer mouse (Peromyscus maniculatus), infected with Sin Nombre virus. Proliferation responses to viral nucleocapsid antigen were relatively weak in T cells isolated from deer mice, regardless of acute or persistent infection. The T cells from acutely infected deer mice synthesized a broad spectrum of cytokines, including IFN-gamma, IL-4, IL-5, and TGF-beta(1), but not TNF, lymphotoxin, or IL-17. However, in T cells from persistently infected deer mice, only TGF-beta(1) was expressed by all lines, whereas some expressed reduced levels of IFN-gamma or IL-5. The Forkhead box P3 transcription factor, a marker of some regulatory T cells, was expressed by most of these cells. Collectively, these data suggest that TGF-beta(1)-expressing regulatory T cells may play an important role in limiting immunopathology in the natural reservoir host, but this response may interfere with viral clearance. Such a response may have arisen as a mutually beneficial coadaptive evolutionary event between hantaviruses and their rodent reservoirs, so as to limit disease while also allowing the virus to persist.
Schountz
Tony
T
School of Biological Sciences, University of Northern Colorado, 1556 Ross Hall, Greeley, CO 80639, USA. tony.schountz@unco.edu
Prescott
Joseph
J
Cogswell
Ann C
AC
Oko
Lauren
L
Mirowsky-Garcia
Katy
K
Galvez
Alejandra P
AP
Hjelle
Brian
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006476:Orthohantavirus / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010542:Peromyscus; D012367:RNA, Viral / Q000378:metabolism; D029261:Sin Nombre virus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D020381:Interleukin-17; D015848:Interleukin-5; D012367:RNA, Viral; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D007371:Interferon-gamma