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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Figure 4

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Donor CD8+ T cells are rapidly recruited to the T cell areas of recipien...
Donor CD8+ T cells are rapidly recruited to the T cell areas of recipient spleens, in direct proximity to host CD11c+ DCs. CFSE-labeled CD8+ T cells (2 × 106) derived from C3H.SW mice (CD45.2+) were intravenously injected into lethally irradiated B6/SJL mice (CD45.1+). (a) Aggregation of CD11c+ DCs in the T cell areas of the spleens of irradiated mice. Cryosections of spleen harvested from lethally irradiated B6 mice 6 hours after TBI were immunostained with anti-CD11c Ab (brown) and anti-CD4 Ab (gray-black). Magnification: top row, ×100; bottom row, ×400. Data are representative of three experiments. (b) Spleens were taken from B6 mice 6 hours after PBS injection and from irradiated B6 mice 6 hours after infusion of CFSE-labeled C3H.SW CD8+ T cells (green) and cryosectioned for immunofluorescent staining with anti-CD11c Ab (red). Magnification, ×100. (c) Splenocytes were prepared and counted at the indicated timepoints. Cells were sequentially labeled with Cychrome-conjugated anti-CD8 Ab coupled with biotinylated anti-CD45.2 and streptavidin-conjugated PE. The percentage of CD8+CD45.2+ cells was obtained by flow cytometry analysis. The recruitment rate (percentage) of donor CD8+ T cells in spleen was calculated by dividing the absolute number of donor CD8+ T cells recovered from the spleens of irradiated recipient mice by the total number of intravenously injected donor CD8+ T cells.