Antigen-specific T-lymphocyte responses in acute and chronic syngeneic graft-versus-host disease

A. D. Hess, C. J. Thoburn, Y. Miura, E. C. Bright

Research output: Contribution to journalArticle

Abstract

Administration of cyclosporine (CyA) following autologous bone marrow transplantation elicits a T-lymphocyte autoaggression syndrome with remarkable similarity to acute and chronic graft-versus-host disease (GVHD). This syndrome termed syngeneic (S) GVHD is mediated by a restricted repertoire of autoreactive T cells that promiscuously recognize major histocompatibility complex (MHC) class II determinants in association with a peptide from the invariant chain (CLIP). The present studies evaluated and compared antigen-specific autoreactive T cells during acute and chronic SGVHD isolated ex vivo with a soluble MHC class II-immunoglobulin (sMHC class II-Ig) molecular construct. Two major subsets were detected that had overlapping specificity recognizing the MHC class II binding domain of CLIP but were differentially dependent on the N- and C-terminal flanking domains of this peptide. Both subsets were detected in acute and chronic SGVHD. Interestingly, the cytokine profiles of the CLIP-reactive T cells closely correlated with the onset and progression of disease. Levels of type 1 cytokines, particularly IFN-γ mRNA production assessed by quantitative polymerase chain reaction (PCR), were dominant during acute SGVHD, whereas chronic SGVHD was associated with type 2 cytokine mRNA production. Although there was a dramatic polarization with respect to cytokine production, only subtle changes in antigen specificity were detected. Of additional interest, autoreactive T cells producing IL-10 mRNA were detected in both acute and chronic SGVHD, suggesting that this cytokine may play an important but perhaps paradoxical role in both the onset and progression of this experimental autoaggression syndrome.

Original languageEnglish (US)
Pages (from-to)53-56
Number of pages4
JournalTransplantation Proceedings
Volume37
Issue number1
DOIs
StatePublished - Jan 2005

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Graft vs Host Disease
Cytokines
T-Lymphocytes
Antigens
Major Histocompatibility Complex
Messenger RNA
Autologous Transplantation
Immunoglobulin Isotypes
Bone Marrow Transplantation
Interleukin-10
Cyclosporine
Disease Progression
Polymerase Chain Reaction
Peptides

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Antigen-specific T-lymphocyte responses in acute and chronic syngeneic graft-versus-host disease. / Hess, A. D.; Thoburn, C. J.; Miura, Y.; Bright, E. C.

In: Transplantation Proceedings, Vol. 37, No. 1, 01.2005, p. 53-56.

Research output: Contribution to journalArticle

Hess, A. D. ; Thoburn, C. J. ; Miura, Y. ; Bright, E. C. / Antigen-specific T-lymphocyte responses in acute and chronic syngeneic graft-versus-host disease. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 1. pp. 53-56.
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