Bystander Sensitization to Activation-Induced Cell Death as a Mechanism of Virus-Induced Immune Suppression
AUTOR(ES)
Zarozinski, Christopher C.
FONTE
American Society for Microbiology
RESUMO
Viral infections which induce strong T-cell responses are often characterized by a period of transient immunodeficiency associated with the failure of host T cells to proliferate in response to mitogens or to mount memory recall responses to other antigens. During acute infections, most of the activated, proliferating virus-specific T cells are sensitized to undergo apoptosis on strong T-cell receptor (TCR) stimulation, but it has not been known why memory T cells not specific for the virus fail to proliferate on exposure to their cognate antigen. Using a lymphocytic choriomeningitis virus (LCMV) infection model in which LCMV-immune Thy 1.1+ splenocytes are adoptively transferred into Thy 1.2+ LCMV carrier mice, we demonstrate here that T cells clearly defined as not specific for the virus are sensitized to undergo activation-induced cell death on TCR stimulation in vitro. This bystander sensitization was in part dependent on the expression of Fas ligand (FasL) on the activated virus-specific cells and gamma interferon (IFN-γ) receptor expression on the bystander T cells. We propose that FasL from highly activated antiviral T cells may sensitize IFN-γ-conditioned T cells not specific for the virus to undergo apoptosis rather than to proliferate on encountering antigen. This may in part explain the failure of memory T cells to respond to recall antigens during acute and persistent viral infections.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=111875Documentos Relacionados
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