We show that the magnitude and duration of the FV-specific CD4+ T cell response is directly proportional to resistance against acute FV infection and subsequent disease, demonstrating a previously unappreciated protective role. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4+ T cells in the absence of a virus-specific CD8+ T cell or B cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility or during coinfection with lactate dehydrogenase-elevating virus (LDV) causes a proportional increase in the number of FV-specific CD4+ T cells required to control FV-induced disease. Furthermore, ultimate failure of FV/LDV coinfected hosts to control FV-induced disease is accompanied by accelerated contraction of the FV-specific CD4+ T cell response. Conversely, a further increased frequency or constant supply of otherwise naïve FV-specific CD4+ T cells is both necessary and sufficient to effectively contain acute infection and prevent disease, even in the presence of coinfection.