Bystander sensitization to activation-induced cell death as a mechanism of virus-induced immune suppression
AuthorsZarozinski, Christopher C.
McNally, James M.
Lohman, Barbara L.
Daniels, Keith A.
Welsh, Raymond M.
UMass Chan AffiliationsDepartment of Molecular Genetics and Microbiology
Graduate School of Biomedical Sciences
Department of Pathology
Document TypeJournal Article
KeywordsAdoptive Transfer; Animals; Antigen-Presenting Cells; *Apoptosis; CD8-Positive T-Lymphocytes; Carrier State; Fas Ligand Protein; Female; *Immune Tolerance; Immunologic Memory; Interferon Type II; *Lymphocyte Activation; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Antigen, T-Cell; Spleen
Medicine and Health Sciences
MetadataShow full item record
AbstractViral 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-gamma) receptor expression on the bystander T cells. We propose that FasL from highly activated antiviral T cells may sensitize IFN-gamma-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.
J Virol. 2000 Apr;74(8):3650-8.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34070