M. Matsumoto et al., Injection of CD4(+) and CD8(+) cells with donor or host accessory cells induces acute graft-vs-host disease in human skin in immunodeficient mice, EXP HEMATOL, 29(6), 2001, pp. 720-727
Objective. We examined cell subsets with respect to cutaneous graft-vs-host
disease by cell sorting selection of subsets of human mononuclear cells an
d injecting the subsets subcutaneously in a mouse model.
Materials and Methods. Cell suspensions containing cultured human epidermal
cells and dermal fibroblasts from a single donor mixed with lymphoid cell
subsets positively selected using the FACSVantage cell sorting instrument a
nd/or MACS cell isolation kits from unrelated individuals were injected int
o immunodeficient mice, This model is known to generate human skin with his
tologic findings similar to human graft-vs-host disease.
Results, Donor T-cell subsets CD4(+) and CD8(+) plus either host or donor C
D14(+) cells were necessary to cause acute cutaneous graft-vs-host disease.
Although graft-vs-host disease can result from recognition of class P anti
gens expressed on human cutaneous cells by donor peripheral blood mononucle
ar cells, additional recognition of class II antigens expressed on host mon
onuclear cells resulted in more severe histologic manifestations. Dendritic
cells that differentiated from donor and host monocytes also showed compet
ent accessory cell function in this system.
Conclusions. Based on this model, human cutaneous graft-vs-host disease was
caused by donor CD4(+) cells and CD8+ cells activated through recognition
of host antigens, including class I and class II antigens presented by eith
er donor or host CD14(+) cells or dendritic cells. (C) 2001 International S
ociety for Experimental Hematology, Published by Elsevier Science Inc.