T cells specific for a polymorphic segment of CD45 induce graft-versus-host disease with predominant pulmonary vasculitis.
To study the character of graft-vs-host disease (GVHD) induced by T cells specific for hemopoietic cells, T cells specific for a polymorphic segment of CD45 were transferred into CD45 congenic mice. C57BL/6 mice that express the CD45b allele were immunized with a 13 mer peptide representing the polymorphic segment (p257-268) of CD45a protein. Conversely, C57BL/6 mice congenic for CD45a were immunized with the CD45b peptide. CD4+ T cells specific for allelic CD45 peptides were elicited. Importantly, T cells specific for CD45 peptides proliferated specifically and vigorously in response to spleen cells expressing the appropriate polymorphic CD45 protein. T cells specific for CD45 induced a substantial graft-vs-host response (GVHR) with predominant early pulmonary vasculitis and later more widespread interstitial mononuclear cell infiltration and alveolitis. No GVHR was induced in bone marrow chimeras expressing only donor hemopoietic cells. Thus, donor T cell recognition of host hemopoietic cells is sufficient to elicit GVHR, but the classical skin, liver, and gut manifestations of GVHD were not observed. The CD45-specific T cells used secreted Th1 cytokines, but without detectable soluble IL-2. Studies using CD45-specific T cells with different effector functions might allow further dissection of donor cell requirements for GVHD syndromes.
Department of Medicine, University of Washington, Seattle 98195, USA.
W
W
Chen
G S
GS
Chatta
W D
WD
Rubin
J G
JG
Clark
R C
RC
Hackman
D K
DK
Madtes
D H
DH
Ligitt
Y
Y
Kusunoki
P J
PJ
Martin
M A
MA
Cheever
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007275:Injections, Intravenous; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D017493:Leukocyte Common Antigens