Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection.
CD4(+) T cells are generally regarded as helpers and regulators of the immune response. Although cytolytic CD4(+) T cells have been described, whether those generated during the course of a viral infection play a role in virus control remains unknown. Here we show that during acute infection with ectromelia virus, the mouse homolog of the human virus of smallpox, large numbers of CD4(+) T cells in the draining lymph node and liver of resistant mice have a cytotoxic phenotype. We also show that these cells kill targets in vivo in a perforin-dependent manner and that mice with specific deficiency of perforin in CD4(+) T cells have impaired virus control. Thus, perforin-dependent CD4(+) T-cell killing of infected cells is an important mechanism of antiviral defense.
Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Min
M
Fang
Nicholas A
NA
Siciliano
Adam R
AR
Hersperger
Felicia
F
Roscoe
Angela
A
Hu
Xueying
X
Ma
Ahamed R
AR
Shamsedeen
Laurence C
LC
Eisenlohr
Luis J
LJ
Sigal
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004481:Ectromelia virus / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D054353:Perforin / Q000276:immunology*
D054353:Perforin