Preterminal host dendritic cells in irradiated mice prime CD8+ T cell–mediated acute graft-versus-host disease
Yi Zhang, … , Adam J. Rivera, Stephen G. Emerson
Yi Zhang, … , Adam J. Rivera, Stephen G. Emerson
Published May 15, 2002
Citation Information: J Clin Invest. 2002;109(10):1335-1344. https://doi.org/10.1172/JCI14989.
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Article Immunology

Preterminal host dendritic cells in irradiated mice prime CD8+ T cell–mediated acute graft-versus-host disease

Abstract

To understand the relationship between host antigen-presenting cells (APCs) and donor T cells in initiating graft-versus-host disease (GVHD), we followed the fate of host dendritic cells (DCs) in irradiated C57BL/6 (B6) recipient mice and the interaction of these cells with minor histocompatibility antigen- (miHA-) mismatched CD8+ T cells from C3H.SW donors. Host CD11c+ DCs were rapidly activated and aggregated in the T cell areas of the spleen within 6 hours of lethal irradiation. By 5 days after irradiation, <1% of host DCs were detectable, but the activated donor CD8+ T cells had already undergone as many as seven divisions. Thus, proliferation of donor CD8+ T cells preceded the disappearance of host DCs. When C3H.SW donor CD8+ T cells were primed in vivo in irradiated B6 mice or ex vivo by host CD11c+ DCs for 24–36 hours, they were able to proliferate and differentiate into IFN-γ–producing cells in β2-microglobulin–deficient (β2m–/–) B6 recipients and to mediate acute GVHD in β2m–/– → B6 chimeric mice. These results indicate that, although host DCs disappear rapidly after allogeneic bone marrow transplantation, they prime donor T cells before their disappearance and play a critical role in triggering donor CD8+ T cell–mediated GVHD.

Authors

Yi Zhang, Jean-Pierre Louboutin, Jiang Zhu, Adam J. Rivera, Stephen G. Emerson

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The activation and proliferation of allogeneic CD8+ T cells depend on th...
The activation and proliferation of allogeneic CD8+ T cells depend on the presence of host DCs and require MHC class I expression on host cells. (a) CFSE-labeled CD8+ T cells (2 × 106) from C3H.SW mice (CD45.2+) were transplanted into irradiated B6 recipients (CD45.1+) at the indicated timepoints after TBI. Five days later, splenocytes were prepared from these mice for flow cytometry analysis as described in Figure 5b legend. (b) C3H.SW CFSE-CD8+CD45.2+ T cells (2 × 106) were intravenously transferred into lethally irradiated β2m–/– mice or congenic B6/SJL (CD45.1+) recipients. Splenocytes were prepared from these mice, and the division of donor CD8+ T cells was analyzed by flow cytometry. The absolute number (c) of C3H.SW CD8+ T cells in the spleens of recipients 5 days after transplantation was calculated based on the flow cytometry analysis. Data shown derive from five independent experiments. One representative experiment of three is shown.