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Perforin-dependent CD4⁺ T-cell cytotoxicity contributes to control a murine poxvirus infection
- Fang, Min, Siciliano, Nicholas A., Hersperger, Adam R., Roscoe, Felicia, Hu, Angela, Ma, Xueying, Shamsedeen, Ahamed R., Eisenlohr, Laurence C., Sigal, Luis J.
- Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.25 pp. 9983-9988
- CD4-positive T-lymphocytes, Ectromelia virus, Variola virus, acute course, cytotoxicity, immune response, infectious diseases, liver, lymph nodes, mice, phenotype, vertebrate viruses, viruses
- 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.