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

From the Department of Hematology, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom (CF, EN, FD); Institute of Hematology, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy (CF, ML)

Correspondence: Francesco Dazzi, MD, PhD, Department of Hematology, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. E-mail: f.dazzi{at}imperial.ac.uk.

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 (T_reg), 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 T_reg after SCT, focusing on the degree of similarity to CD4⁺CD25^– conventional T cells (T_conv).

Design and Methods: We assessed the TCR Vß repertoire of T_reg 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 T_reg and T_conv.

Results: For up to 3 years after SCT the repertoires of T_reg and T_conv 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 T_conv but not in T_reg.

Interpretation and Conclusions: Our data show that the TCR repertoires of T_reg and T_conv 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.

Key words: T-cell receptor repertoire, regulatory T cells, allogeneic stem cell transplantation.

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