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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.