Reconstitution of γδ T cell repertoire diversity after human allogeneic hematopoietic cell transplantation and the role of peripheral expansion of mature T cell population in the graft

Abstract

Summary:We have examined the reconstitution of ␥␦ T cell repertoire diversity after human allogeneic hematopoietic cell transplantation using a polymerase chain reaction (PCR)-based complementarity-determining region (CDR) 3 size spectratyping and DNA sequencing. The CDR3 complexity in the variable region of the T cell receptor (TCR)-␦ chain was different amongst the individuals studied. Furthermore, CDR3 size distribution patterns of allogeneic hematopoietic cell transplant recipients were almost completely recovered by a few months after transplantation. In some patients, clonal predominance of the TCRDV1+ T cells became evident during the period after transplantation. In one particular donor/recipient pair, clonal predominance of TCRDV1+ T cells was already present in blood lymphocytes of the donor, and was also observed in the recipient after transplantation. Using this donor/recipient pair, we have questioned whether ␥␦ T cell regeneration occurs via the peripheral expansion of mature T cells in the graft. In the donor lymphocytes, two expanding ␥␦ T cell clones, which were demonstrated by CDR3 sequences of the TCR-␦ chain, were recognized. These two clones were identified in the T cells from the recipient post transplant, but not before transplantation. One of the two clones was still detectable 1. years after the transplant procedure. These results strongly suggest that peripheral expansion of mature T cells in the graft is the principal pathway of ␥␦ T cell regeneration after allogeneic hematopoietic cell transplantation in adults. Bone Marrow Transplantation (2000) 26, 177-185. Keywords: T cell receptor; ␦-chain; diversity; transplantation High-dose chemoradiotherapy depletes T cells in blood and marrow transplant recipients and adequate T cell regeneration is essential for successful transplantation. The repertoire of T cells requires to be sufficiently diverse in order to recognize a wide range of microorganism-derived antigens. ␣␤ T cells are almost exclusively thymus-dependent

A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors

“…47 The predominant mechanism of gd reconstitution seems to be peripheral expansion of donor gd clones, which can persist for more than 1.5 years after transplantation. 48 Unlike ab T cells, gd T cells can reconstitute via an alternative, thymusindependant pathway. 49,50 However, the precise regulatory and cytotoxic functions of gd T cells after transplantation are not fully understood, and further investigation is required to define the role and importance of gd T cells as potential targets for post transplantation immunotherapy.…”

Extensive clonal expansion of T lymphocytes causes contracted diversity of complementarity-determining region 3 and skewed T cell receptor repertoires after allogeneic hematopoietic cell transplantation

“…2,3 We also found that TCR usage appears to be limited, and that amino acid sequences frequently contain an arginine residue followed by acidic amino acid residues in the complementarity-determining region 3 (CDR3) of TCR-␤ chains containing BV24S1, suggesting that skewing of the TCRAV and TCRBV repertoires is antigen-driven. 1 These features of post-transplant T cell regeneration are similar to those during extrathymic differentiation of T cell progenitors and peripheral expansion of mature T cell populations, which have been demonstrated by murine bone marrow transplantation studies.…”

“…The PCR products of the TCR-␤ chain were cloned into the PCR2.1 TA cloning vector (Invitrogen, Carlsbad, CA, USA) and sequenced using a Big-Dye Terminator Cycle Sequencing Kit (Perkin-Elmer Applied Biosystems) 3 and an Applied Biosystems 377A automated DNA sequencer.…”

Effects of Immunotherapy on the Distribution and Clonality of TCR Vγ and Vδ Subfamily T Cells in Allergic Rhinitis Patients

“…Studies also reveal TCR gd T cells can be classified into Th1 cells and Th2 cells. In the different stages of respiratory allergic inflammation, different TCR gd T cells exert positive or negative regulatory effects on the immune function, and specific immunotherapy (SIT) can rectify the imbalance between T cell subsets (3)(4)(5)(6)(7)(8). The knowledge on TCR gd T cells is still insufficient as compared to TCR ab T cells, and few studies report the role of TCR gd T cells in allergic rhinitis (AR) and SIT.…”

“…Ten AR patients undergoing SIT with house-dust-mite extract for 1 year were recruited. Quanti tative analysis of immunofluorescence was performed to detect the serum specific IgE (sIgE) level before and after SIT; RT-PCR-genescan analysis was employed to detect the mRNA expressions of TCR Vg (I-III) and Vd (1)(2)(3)(4)(5)(6)(7)(8) in the peripheral mononuclear cells followed by analysis of T cell clonality. Real-time quantitative PCR was applied to detect the expressions of TCR Vg I-III genes.…”