T cell receptor-gamma/delta cells protect mice from herpes simplex virus type 1-induced lethal encephalitis.
Increased numbers of T cell receptor (TCR)-gamma/delta cells have been observed in animal models of influenza and sendai virus infections, as well as in patients infected with human immunodeficiency virus and herpes simplex virus type 1 (HSV-1). However, a direct role for TCR-gamma/delta cells in protective immunity for pathogenic viral infection has not been demonstrated. To define the role of TCR-gamma/delta cells in anti-HSV-1 immunity, TCR-alpha-/- mice treated with anti- TCR-gamma/delta monoclonal antibodies or TCR-gamma/delta x TCR-alpha/beta double-deficient mice were infected with HSV-1 by footpad or ocular routes of infection. In both models of HSV-1 infection, TCR-gamma/delta cells limited severe HSV-1-induced epithelial lesions and greatly reduced mortality by preventing the development of lethal viral encephalitis. The observed protection resulted from TCR-gamma/delta cell-mediated arrest of both viral replication and neurovirulence. The demonstration that TCR-gamma/delta cells play an important protective role in murine HSV-1 infections supports their potential contribution to the immune responses in human HSV-1 infection. Thus, this study demonstrates that TCR-gamma/delta cells may play an important regulatory role in human HSV-1 infections.
Sciammas
R
R
Ben May Institute for Cancer Research, Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
Kodukula
P
P
Tang
Q
Q
Hendricks
R L
RL
Bluestone
J A
JA
D000818:Animals; D018792:Encephalitis, Viral / Q000276:immunology* / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D018139:Simplexvirus / Q000472:pathogenicity / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D012668:Trigeminal Ganglion / Q000166:cytology; D014779:Virus Replication
D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma