Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung
AuthorsChen, Hong D.
Fraire, Armando E.
Brehm, Michael A.
Welsh, Raymond M.
Selin, Liisa K.
UMass Chan AffiliationsDepartment of Molecular Genetics and Microbiology
Department of Pathology
Graduate School of Biomedical Sciences
Document TypeJournal Article
KeywordsAdministration, Intranasal; Animals; Antigens, Viral; CD8-Positive T-Lymphocytes; Cells, Cultured; Cytokines; Humans; Immunization; *Immunologic Memory; Interferon Type II; Lung; Lymphocyte Activation; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C57BL; Nasal Mucosa; Organ Specificity; Respiratory Tract Infections; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic; Vaccinia; Vaccinia virus
Medicine and Health Sciences
MetadataShow full item record
AbstractA potent role for memory CD8+ T cells in heterologous immunity was shown with a respiratory mucosal model of viral infection. Memory CD8+ T cells generated after lymphocytic choriomeningitis virus (LCMV) infection were functionally activated in vivo to produce interferon-gamma (IFN-gamma) during acute infection with vaccinia virus (VV). Some of these antigen-specific memory cells selectively expanded in number, which resulted in modulation of the original LCMV-specific T cell repertoire. In addition, there was an organ-selective compartmental redistribution of these LCMV-specific T cells during VV infection. The presence of these LCMV-specific memory T cells correlated with enhanced VV clearance, decreased mortality and marked changes in lung immunopathology. Thus, the participation of pre-existing memory T cells specific to unrelated agents can alter the dynamics of mucosal immunity and disease course in response to a pathogen.
SourceNat Immunol. 2001 Nov;2(11):1067-76. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33484
Related ResourcesLink to article in PubMed
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Independent regulation of lymphocytic choriomeningitis virus-specific T cell memory pools: relative stability of CD4 memory under conditions of CD8 memory T cell lossVarga, Steven Michael; Selin, Liisa K.; Welsh, Raymond M. (2001-02-13)Infection of mice with a series of heterologous viruses causes a reduction of memory CD8(+) T cells specific to viruses from earlier infections, but the fate of the virus-specific memory CD4(+) T cell pool following multiple virus infections has been unknown. We have previously reported that the virus-specific CD4(+) Th precursor (Thp) frequency remains stable into long-term immunity following lymphocytic choriomeningitis virus (LCMV) infection. In this study, we questioned whether heterologous virus infections or injection with soluble protein CD4 Ags would impact this stable LCMV-specific CD4(+) Thp memory pool. Limiting dilution analyses for IL-2-producing cells and intracellular cytokine staining for IFN-gamma revealed that the LCMV-specific CD4(+) Thp frequency remains relatively stable following multiple heterologous virus infections or protein Ag immunizations, even under conditions that dramatically reduce the LCMV-specific CD8(+) CTL precursor frequency. These data indicate that the CD4(+) and CD8(+) memory T cell pools are regulated independently and that the loss in CD8(+) T cell memory following heterologous virus infections is not a consequence of a parallel loss in the memory CD4(+) T cell population.
Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulationKim, Sung-Kwon; Brehm, Michael A.; Welsh, Raymond M.; Selin, Liisa K. (2002-06-22)By examining adoptively transferred CSFE-labeled lymphocytic choriomeningitis virus (LCMV)-immune donor T cells in Thy-1 congenic hosts inoculated with viruses or with the cytokine inducer poly(I:C), strikingly different responses of bona fide memory T cells were found in response to different stimuli. Poly(I:C) (cytokine) stimulation caused a limited synchronized division of memory CD8 T cells specific to each of five LCMV epitopes, with no increase and sometimes a loss in number, and no change in their epitope hierarchy. Homologous LCMV infection caused more than seven divisions of T cells specific for each epitope, with dramatic increases in number and minor changes in hierarchy. Infections with the heterologous viruses Pichinde and vaccinia (VV) caused more than seven divisions and increases in number of T cells specific to some putatively cross-reactive but not other epitopes and resulted in substantial changes in the hierarchy of the LCMV-specific T cells. Hence, there can be memory T cell division without proliferation (i.e., increase in cell number) in the absence of Ag and division with proliferation in the presence of Ag from homologous or heterologous viruses. Heterologous protective immunity between viruses is not necessarily reciprocal, given that LCMV protects against VV but VV does not protect against LCMV. VV elicited proliferation of LCMV-induced CD8 and CD4 T cells, whereas LCMV did not elicit proliferation of VV-induced T cells. Thus, depending on the pathogen and the sequence of infection, a heterologous agent may selectively stimulate the memory pool in patterns consistent with heterologous immunity.
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