Adoptive CD8 T Cell Control of Pathogens Cannot Be Improved by Combining Protective Epitope Specificities
Adoptive transfer of CD8 T cells has the potential to cure infectious or malignant diseases that are refractory to conventional chemotherapy. A practically important but still unanswered question is whether mixtures of protective CD8 T cells with different epitope specificities mediate more efficient effector cell functions than do the monospecific individual CD8 T cell populations. In this study, we have addressed this issue for models of viral and bacterial infection. CD8 T cell-mediated cytotoxicity in vitro and protection in vivo were assessed to test whether CD8 T cell lines cooperate in target cell lysis and control of infection, respectively. Our data clearly show that mixtures of cy…
Dynamic Antigen Presentation Patterns of Listeria monocytogenes-Derived CD8 T Cell Epitopes In Vivo
Abstract Little information exists regarding the presentation of antigenic peptides in infected tissues. In this study the in vivo presentation of four different CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide presentation was measured by a new, highly sensitive, ex vivo Ag presentation assay that was based on the testing of freshly isolated cells from infected spleens with peptide-specific CD8 T cell lines in an IFN-γ-specific ELISPOT assay. Remarkably, the peptide presentation pattern of splenocytes and that of macrophages purified from spleens of L. monocytogenes-infected mice were different from those of in vitro infected macrophage-like cell lines. The in vivo Ag p…
Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus
ABSTRACTThe mouse cytomegalovirus (MCMV)m152- andm06-encoded glycoproteins gp40 and gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MCMV infection in fibroblasts. As a result, presentation of an immediate-early protein pp89-derived nonapeptide toH-2Ld-restricted CD8+cytotoxic T cells is completely prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone marrow macrophages and the macrophage cell line J774 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of them152andm06genes in macr…
The Putative Natural Killer Decoy Early Genem04(gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T Cells
ABSTRACTSeveral early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, them152gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the “missing self.” The retention, however, is counteracted by them04early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 mi…
Control of murine cytomegalovirus in the lungs: Relative but not absolute immunodominance of the immediate-early 1 nonapeptide during the antiviral cytolytic T-lymphocyte response in pulmonary infiltrates
Effective control by the immune system is a hallmark of cytomegalovirus (CMV) infection. Accordingly, human CMV disease is a medical problem restricted to the immunologically immature or immunocompromised host (for a review, see reference 21). Murine models have implicated natural killer (NK) cells and CD8 T cells in the control of CMV infection. While NK cells mediate early protection in genetically resistant mouse inbred strains (4, 5, 31, 51), CD8 T cells establish enduring protective memory and function as principal antiviral effectors in susceptible strains (31). Specifically, in the BALB/c strain, major histocompatibility complex (MHC) class I-restricted antiviral CD8 T cells resolve …