Antigen presentation by nonhemopoietic cells amplifies clonal expansion of effector CD8 T cells in a pathogen-specific manner.
Professional APCs of hemopoietic-origin prime pathogen-specific naive CD8 T cells. The primed CD8 T cells can encounter Ag on infected nonhemopoietic cell types. Whether these nonhemopoietic interactions perpetuate effector T cell expansion remains unknown. We addressed this question in vivo, using four viral and bacterial pathogens, by comparing expansion of effector CD8 T cells in bone marrow chimeric mice expressing restricting MHC on all cell types vs mice that specifically lack restricting MHC on nonhemopoietic cell types or radiation-sensitive hemopoietic cell types. Absence of Ag presentation by nonhemopoietic cell types allowed priming of naive CD8 T cells in all four infection models tested, but diminished their sustained expansion by approximately 10-fold during lymphocytic choriomeningitis virus and by < or =2-fold during vaccinia virus, vesicular stomatitis virus, or Listeria monocytogenes infections. Absence of Ag presentation by a majority (>99%) of hemopoietic cells surprisingly also allowed initial priming of naive CD8 T cells in all the four infection models, albeit with delayed kinetics, but the sustained expansion of these primed CD8 T cells was markedly evident only during lymphocytic choriomeningitis virus, but not during vaccinia virus, vesicular stomatitis virus, or L. monocytogenes. Thus, infected nonhemopoietic cells can amplify effector CD8 T cell expansion during infection, but the extent to which they can amplify is determined by the pathogen. Further understanding of mechanisms by which pathogens differentially affect the ability of nonhemopoietic cell types to contribute to T cell expansion, how these processes alter during acute vs chronic phase of infections, and how these processes influence the quality and quantity of memory cells will have implications for rational vaccine design.
Thomas
Sunil
S
Department of Immunology and Washington National Primate Center, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.
Kolumam
Ganesh A
GA
Murali-Krishna
Kaja
K
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D002999:Clone Cells; D007239:Infections / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008089:Listeria monocytogenes; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014616:Vaccinia virus; D014721:Vesicular stomatitis Indiana virus
D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin