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


METHODS
We assessed the TCR Vbeta 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 Vbeta 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 Vbeta 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 Vbeta expressing an oligoclonal profile in Tconv but not in Treg.


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.
Fozza
Claudio
C
Department of Hematology, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Nadal
Elisabet
E
Longinotti
Maurizio
M
Dazzi
Francesco
F
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous
D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell