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T-cell receptor repertoire usage after allografting differs between CD4+CD25+ regulatory T cells and their CD4+CD25- counterpart

Fozza, Claudio and Nadal, Elisabet and Longinotti, Maurizio Roberto and Dazzi, Francesco (2007) T-cell receptor repertoire usage after allografting differs between CD4+CD25+ regulatory T cells and their CD4+CD25- counterpart. Haematologica, Vol. 92 (2), p. 206-214. eISSN 1592-8721. Article.

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DOI: 10.3324/haematol.10774

Abstract

Background and Objectives: After allogeneic haematopoietic stem cell transplantation (SCT) the whole T-cell receptor (TCR) repertoire shows a markedly skewed pattern for 2–3 years. A small fraction of CD4+T cells is represented by CD25+ regulatory lymphocytes (Treg), which play a crucial role in modulating peripheral tolerance. To investigate their ability to react to the massive antigenic stimulation generated in an allogeneic host, which could significantly affect their pattern of reconstitution, we analyzed the TCR repertoire of Treg after SCT, focusing on the degree of similarity to CD4+CD25-conventional T cells (Tconv).
Design and Methods: We assessed the TCR Vß repertoire of Treg in ten patients who had received allogeneic SCT, by using complementarity determining region 3 (CDR3) spectratyping. We developed a new similarity score for the analysis. This score expresses the proportion of Vß with similar profile between Treg and Tconv.
Results: For up to 3 years after SCT the repertoires of Treg and Tconv were characterized by several Vß with different profiles between the two cell subsets, while they were extremely similar in patients more than 3 years post-allografting (similarity score= 0.90 vs. 0.61). The differences observed early after SCT were mainly ascribable to Vß expressing an oligoclonal profile in Tconv but not in Treg.
Interpretation and Conclusions: Our data show that the TCR repertoires of Treg and Tconv are significantly different early post-SCT, while they tend to become identical with full reconstitution. This difference could reflect either a discrepancy in the in vivo reactivity against common antigenic stimulations or be the result of different post-transplant ontogeny.

Item Type:Article
ID Code:4420
Status:Published
Refereed:Yes
Uncontrolled Keywords:T-cell receptor repertoire, regulatory T cells, allogeneic stem cell transplantation
Subjects:Area 06 - Scienze mediche > MED/15 Malattie del sangue
Divisions:001 Università di Sassari > 03 Istituti > Ematologia
Publisher:Ferrata Storti Foundation
eISSN:1592-8721
Deposited On:31 Aug 2010 17:37

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