Alloreactive T cells develop in the very early period following human stem cell transplantation and are characterised by a range of novel features

Abstract

Abstract Allogeneic stem cell transplantation can cure some patients with hematopoietic malignancy but relies on development of a donor T cell alloreactive immune response which develops very early but is difficult to study due to intense lymphopenia. We characterised the phenotype and functional profile of T cells at day 14 in patients undergoing transplantation. T cells were present at very low number but displayed intense proliferation with strong cytokine production. Oligoclonal expansions at day 14 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 rapidly drives naïve T cells towards a unique phenotype characterised by intense functional activation. Moreover they demonstrate that early clonal T cell responses are recruited to sites of subsequent tissue damage and provide a range of novel targets for potential therapeutic immunomodulation.