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J. Virol., 08 1995, 4914-4923, Vol 69, No. 8
ZC Neal and GA Splitter
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.
Copyright © 1995, American Society for Microbiology
Picornavirus-specific CD4+ T lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies
Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison 53706, USA.
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