Unique features and clinical importance of acute alloreactive immune responses.

Autor:	Inman CF; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Eldershaw SA; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Croudace JE; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Davies NJ; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Sharma-Oates A; Centre for Computational Biology, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom., Rai T; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Pearce H; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Sirovica M; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Chan YLT; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Verma K; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Zuo J; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Nagra S; Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom., Kinsella F; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and., Nunnick J; Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom., Amel-Kashipaz R; Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom., Craddock C; Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom., Malladi R; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and.; Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom., Moss P; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, and.; Birmingham Health Partners, Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2018 May 17; Vol. 3 (10). Date of Electronic Publication: 2018 May 17 (Print Publication: 2018).
DOI:	10.1172/jci.insight.97219
Abstrakt:	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.
Databáze:	MEDLINE
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