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 receptorrepertoire

We have previously reported that skewed repertoires of T cell receptor-beta chain variable region (TCRBV) and TCR-alpha chain variable region (TCRAV) are observed at an early period after allogeneic hematopoietic cell transpl antation. Furthermore, we found that T lymphocytes using TCRBV24S1 were inc reased in 28% of the recipients of allogeneic grafts and an increase of TCR BV24S1 usage was shown to result from clonal expansions, Interestingly, the arginine residue was frequently present at the 3 ' terminal of BV24S1 segm ent and was followed by an acidic amino acid residue within the CDR3 region . These results suggest that these clonally expanded T cells are not random ly selected, but are expanded by stimulation with specific antigens, This s tudy was undertaken to elucidate the mechanisms of the posttransplant skewi ng of TCR repertoires, Since the CD8(+)CD28(-)CD57(+) T cell subset has bee n reported to expand in the peripheral blood of patients receiving allogene ic hematopoietic cell grafts, we examined the TCRAV and TCRBV repertoires o f the CD8(+)CD28(-) T cell and CD8(+)CD28(+) T cell subsets, and also deter mined the clonality of both T cell populations, In all three recipients exa mined, the CD8+CD28- T cell subset appeared to define the post-transplant T CR repertoire of circulating blood T cells. Moreover, the CDR3 length of TC RBV imposed constraints in both CD8+CD28- T cell and CD8(+)CD28(+) T cell s ubsets. The DNA sequences of the CDR3 region were determined, and the same clones were identified within both CD8(+)CD28(-) and CD8(+)CD28(-) T cell s ubsets in the same individuals. These results suggest that the clonally exp anded 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 skew-ed TCR repertoire.