Identification of the T cell clones expanding within both CD8+CD28+ and CD8+CD28− T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire

Abstract

We have previously reported that skewed repertoires of T cell receptor-β chain variable region (TCRBV) and TCR-α chain variable region (TCRAV) are observed at an early period after allogeneic hematopoietic cell transplantation. Furthermore, we found that T lymphocytes using TCRBV24S1 were increased in 28% of the recipients of allogeneic grafts and an increase of TCRBV24S1 usage was shown to result from clonal expansions. Interestingly, the arginine residue was frequently present at the 3′ terminal of BV24S1 segment and was followed by an acidic amino acid residue within the CDR3 region. These results suggest that these clonally expanded T cells are not randomly selected, but are expanded by stimulation with specific antigens. This study was undertaken to elucidate the mechanisms of the post-transplant skewing of TCR repertoires. Since the CD8⁺CD28⁻CD57⁺ T cell subset has been reported to expand in the peripheral blood of patients receiving allogeneic hematopoietic cell grafts, we examined the TCRAV and TCRBV repertoires of the CD8⁺CD28⁻ T cell and CD8⁺CD28⁺ T cell subsets, and also determined the clonality of both T cell populations. In all three recipients examined, the CD8⁺CD28⁻ T cell subset appeared to define the post-transplant TCR repertoire of circulating blood T cells. Moreover, the CDR3 length of TCRBV imposed constraints in both CD8⁺CD28⁻ T cell and CD8⁺CD28⁺ T cell subsets. The DNA sequences of the CDR3 region were determined, and the same clones were identified within both CD8⁺CD28⁻ and CD8⁺CD28⁺ T cell subsets in the same individuals. These results suggest that the clonally expanded CD8⁺CD28⁻ T cells after allogeneic hematopoietic cell transplantation derive from the CD8⁺CD28⁺ T cell subset, possibly by an antigen-driven mechanism, resulting in the skewed TCR repertoire. Bone Marrow Transplantation (2001) 27, 731–739.