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Department of Immunology and Washington National Primate Center, University of Washington, Seattle, WA 98195
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 
10-fold during lymphocytic choriomeningitis virus and by 
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institutes of Health Grants 1R01AI053146 and R21AI051386 (to K.M.-K.) and by funds from the Washington National Primate Center and the University of Washington Department of Immunology.
2 Address correspondence and reprint requests to Dr. Kaja Murali-Krishna, Department of Immunology and Washington National Primate Center, Box 357650 HSB, 1959 Northeast Pacific Street, Seattle, WA 98195. E-mail address: mkaja{at}u.washington.edu
3 Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; 
2m, 2-microglobulin; Lm, Listeria monocytogenes; VSV, vesicular stomatitis virus; VV, vaccinia virus.
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