Visualization, fate, and pathogenicity of antigen-specific CD8+ T cells in the graft-versus-host reaction.
To follow the fate of alloreactive T cell effectors in graft-vs-host disease, Ld-specific CD8+ T cells from C57BL/6 2C TCR-transgenic donors were transplanted into sublethally irradiated (750 cGy) Ld+ or Ld- recipients. In Ld- C57BL/6 or (BALB/c-dm2 x C57BL/6)F1 recipients, naive 2C T cells engrafted and survived long term, but did not acquire effector function. In Ld+ (BALB/c x C57BL/6)F1 recipients, 2C T cells engrafted, expanded, became cytolytic, destroyed host B cells and double-positive thymocytes, and later disappeared. Despite marked damage to lymphoid and hemopoietic cells by 2C T cells, no significant pathology was detected in other organs, and recipients survived. Ld+ (BALB/c x C57BL/6)F1 recipients died when LPS/endotoxin was administered on day 7 after cell transfer, while Ld- (BALB/c-dm2 x C57BL/6)F1 recipients survived. Our findings show that under certain conditions, a CD8+ T cell population recognizing an extremely limited repertoire of Ags can initiate graft-vs-host disease.
Yu
X Z
XZ
Division of Clinical Research, Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98105, USA.
Bidwell
S
S
Martin
P J
PJ
Anasetti
C
C
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006086:Graft vs Host Disease / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000401:mortality; D006087:Graft vs Host Reaction / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D007275:Injections, Intravenous; D007519:Isoantigens / Q000008:administration & dosage / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007519:Isoantigens; D008070:Lipopolysaccharides; D011948:Receptors, Antigen, T-Cell