The Journal of Experimental Medicine
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Published online 16 October 2000.
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© The Rockefeller University Press, 0022-1007/2000/10/1135/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 8, October 16, 2000 1135-1142

Original Article

Requirements for Bone Marrow–Derived Antigen-Presenting Cells in Priming Cytotoxic T Cell Responses to Intracellular Pathogens

Laurel L. Lenza, Eric A. Butza, and Michael J. Bevana

a Department of Immunology and the Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195
Department of Immunology and Howard Hughes Medical Institute, School of Medicine, Box 357370, University of Washington, Seattle, WA 98195.206-685-3612206-685-3610

Bone marrow (BM)-derived antigen-presenting cells (APCs) are potent stimulators of T cell immune responses. We investigated the requirements for antigen presentation by these cells in priming cytotoxic T lymphocyte (CTL) responses to intracellular bacterial and viral pathogens. [Parent->F1] radiation BM chimeras were constructed using C57BL/6 donors and (C57BL/6 x BALB/c)F1 recipients. Infection of chimeric mice with either Listeria monocytogenes or vaccinia virus expressing the nucleoprotein (NP) antigen from lymphocytic choriomeningitis virus (LCMV) primed H2-Db–restricted, but not H2-Kd–restricted CTL responses, demonstrating the requirement for BM-derived APCs for successful priming of CTL responses to these pathogens. Surprisingly, this did not hold true for chimeric mice infected with LCMV itself. LCMV-infected animals developed strong CTL responses specific for both H2-Db– and H2-Ld–restricted NP epitopes. These findings indicate that in vivo priming of CTL responses to LCMV is remarkably insensitive to deficiencies in antigen presentation by professional BM-derived APCs.

Key Words: cross-presentation • cytotoxic T cell • bacterial immunity • viral immunity • radiation chimera

L.L. Lenz's present address is the Department of Molecular and Cell Biology, 401 Barker Hall, University of California at Berkeley, Berkeley, CA 94720-3202. E.A. Butz's present address is Immunex Corporation, 51 University St., Seattle, WA 98101.

Abbreviations used in this paper: B6, C57BL/6; BM, bone marrow; CB6, (BALB/c x B6)F1; DC, dendritic cell; LCMV, lymphocytic choriomeningitis virus; LLO, listeriolysin O; NP, nucleoprotein; VacNP, vaccinia virus expressing LCMV NP.

© 2000 The Rockefeller University Press


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