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Characterization of T-cell clones derived from peripheral blood lymphocytes
of a patient with transfusion-associated graft-versus-host disease:
Fas-mediated killing by CD4+ and CD8+ cytotoxic T-cell clones and tumor
necrosis factor beta production by CD4+ T-cell clones
M Nishimura, S Uchida, S Mitsunaga, Y Yahagi, K Nakajima, K Tadokoro and T Juji
Department of Research, The Japanese Red Cross, Central Blood Center,
Tokyo.
Transfusion-associated graft-versus-host disease (TA-GVHD) is one of the
most serious adverse effects of blood transfusion. It is generally thought
to be caused by the infused lymphocytes. Donor-derived cytotoxic T
lymphocytes (CTLs) directed against the recipient's HLAs, which have
escaped the recipient's immune system and are proliferating, are considered
to attack recipient organs and tissues. Despite the seriousness of the
disease, the precise mechanism of its development remains unclear and no
definitive treatment has been developed. With the aim of developing an
effective treatment, we established and characterized T-cell clones from
peripheral blood lymphocytes (PBLs) of a TA-GVHD patient. Three types of
clones were established. Type I clones were CD8+ and specifically lyse
cells that express HLA B52. Type II clones were CD4+, specifically lysed
cells that express HLA DR15, and proliferated in response to stimulation
with cells that express DR15. Type III clones were also CD4+, showed no
cytotoxic activity toward any HLA-expressing cells, and proliferated in
response to stimulation with cells that express DR15. Furthermore, we found
that the Fas/Fas-ligand (Fas-L) system is involved in the cytotoxicity of
the type I and II clones and that the type III clones produce and secrete a
large amount of tumor necrosis factor beta (TNFbeta) after antigen
stimulation. Based on our results, these three types of clones can be
classified into two categories: those that have the ability to induce GVHD
directly by cytolysis and that show no cytotoxic activity and those that
have the ability to cause GVHD indirectly through secretion of cytotoxic
lymphokines.
Volume 89,
Issue 4,
pp. 1440-1445,
02/15/1997
Copyright © 1997 by The American Society of Hematology

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