Unique features and clinical importance of acute alloreactive immune responses

Research output: Contribution to journalArticle

Authors

External organisations

  • Institute for Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, England, UK.
  • Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital

Abstract

Allogeneic stem cell transplantation (allo-SCT) can cure some patients with hematopoietic malignancy, but this relies on the development of a donor T cell alloreactive immune response. T cell activity in the first 2 weeks after allo-SCT is crucial in determining outcome, despite the clinical effects of the early alloreactive immune response often not appearing until later. However, the effect of the allogeneic environment on T cells is difficult to study at this time point due to the effects of profound lymphopenia. We approached this problem by comparing T cells at week 2 after allograft to T cells from autograft patients. Allograft T cells were present in small numbers but displayed intense proliferation with spontaneous cytokine production. Oligoclonal expansions at week 2 came to represent a substantial fraction of the established T cell pool and were recruited into tissues affected by graft-versus-host disease. Transcriptional analysis uncovered a range of potential targets for immune manipulation, including OX40L, TWEAK, and CD70. These findings reveal that recognition of alloantigen drives naive T cells toward a unique phenotype. Moreover, they demonstrate that early clonal T cell responses are recruited to sites of subsequent tissue damage and provide a range of targets for potential therapeutic immunomodulation.

Details

Original languageEnglish
Article numbere97219
JournalJCI Insight
Volume3
Issue number10
Early online date17 May 2018
Publication statusPublished - 2018

Keywords

  • Journal Article