Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies.

Picornaviruses are a family of positive-strand RNA viruses that are responsible for a variety of devastating human and animal diseases. An attenuated strain of mengovirus (vMC24) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (EMCV). Immunogen-specific stimulation of vMC24-immune splenocytes in vitro demonstrates preferential activation of CD4+ lymphocytes. vMC24-immune splenocytes adoptively transferred to naive recipients conferred protection against lethal EMCV challenge. Immune splenocytes, expanded in vitro, were > 92% CD4+ T lymphocytes. Interestingly, adoptive transfer of these expanded cells engendered protection against lethal challenge. In vivo depletion of CD4+ T lymphocytes prior to lethal challenge abrogated survival of transfer recipients, confirming that CD4+ T lymphocytes were essential for protection. Subsequent rechallenge of vMC24-immune splenocyte recipients with a greater EMCV dose elicited serum neutralizing antibody titers paralleling the high titers observed in vMC24-immunized mice. Unexpectedly, an augmented humoral response was absent in vMC24-specific CD4+ T-cell recipients after the secondary challenge. Moreover, comparably low serum neutralizing antibody titers failed to protect passive transfer recipients when correspondingly challenged. vMC24-immune splenocytes expanded in vitro (> 94% CD4+) lysed vMC24-infected A20.J target cells. The ability to transfer protection with primed CD4+ T cells, in the absence of primed B lymphocytes or immune sera, is novel for picornaviral infections. Consequently, mechanisms such as CD4+ cytolytic T-lymphocyte activity are implicated in mediating protection.