γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease.
Chikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. Because CHIKV is initially introduced via the skin, where γδ T cells are prevalent, we evaluated the response of these cells to CHIKV infection. CHIKV infection led to a significant increase in γδ T cells in the infected foot and draining lymph node that was associated with the production of proinflammatory cytokines and chemokines in C57BL/6J mice. γδ T cell(-/-) mice demonstrated exacerbated CHIKV disease characterized by less weight gain and greater foot swelling than occurred in wild-type mice, as well as a transient increase in monocytes and altered cytokine/chemokine expression in the foot. Histologically, γδ T cell(-/-) mice had increased inflammation-mediated oxidative damage in the ipsilateral foot and ankle joint compared to wild-type mice which was independent of differences in CHIKV replication. These results suggest that γδ T cells play a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage.


OBJECTIVE
Recent epidemics, including the 2004 to 2007 outbreak and the spread of CHIKV to naive populations in the Caribbean and Central and South America with resultant cases imported into the United States, have highlighted the capacity of CHIKV to cause explosive epidemics where the virus can spread to millions of people and rapidly move into new areas. These studies identified γδ T cells as important to both recruitment of key inflammatory cell populations and dampening the tissue injury due to oxidative stress. Given the importance of these cells in the early response to CHIKV, this information may inform the development of CHIKV vaccines and therapeutics.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA kristin_long@unc.edu.
Kristin M
KM
Long
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Martin T
MT
Ferris
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Alan C
AC
Whitmore
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Stephanie A
SA
Montgomery
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Lance R
LR
Thurlow
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Charles E
CE
McGee
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
Carlos A
CA
Rodriguez
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
Jean K
JK
Lim
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Mark T
MT
Heise
D000818:Animals; D001835:Body Weight; D065632:Chikungunya Fever / Q000276:immunology*; D002646:Chikungunya virus / Q000276:immunology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000473:pathology; D006651:Histocytochemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta