PMID- 23396243 OWN - NLM STAT- MEDLINE DCOM- 20140314 LR - 20130416 IS - 1523-6536 (Electronic) IS - 1083-8791 (Linking) VI - 19 IP - 5 DP - 2013 May TI - Long-term immune reconstitution of naive and memory t cell pools after haploidentical hematopoietic stem cell transplantation. PG - 703-12 LID - S1083-8791(13)00053-0 [pii] LID - 10.1016/j.bbmt.2013.01.017 [doi] AB - Haploidentical hematopoietic stem cell transplantation (HSCT) constitutes an important alternative for patients lacking a human leukocyte antigen (HLA)-matched donor. Although the use of haploidentical donors is increasingly common, the long-term impact of generating a donor-derived immune system in the context of an HLA-mismatched thymic environment remains poorly characterized. We performed an in-depth assessment of immune reconstitution in a group of haploidentical HSCT recipients 4 to 6 years posttransplantation, in parallel with the respective parental donors and age-matched healthy control subjects. Our data show that the proportion of naive and memory subsets in the recipients, both within CD8(+) and CD4(+) T cells, more closely resembled that observed in age-matched control subjects than in the donors. HSCT recipients displayed relatively high signal-joint T cell-receptor excision circle levels and a high frequency of the recent thymic emigrant-enriched CD31(+) subset within naive CD4(+) and naive regulatory T cells. Moreover, CD8(+), CD4(+), and regulatory T cells from HSCT recipients displayed a diverse T cell repertoire. These results support a key role for thymic output in T cell reconstitution. Nevertheless, HSCT recipients had significantly shorter telomeres within a naive-enriched CD4(+) T cell population than age-matched control subjects, despite the similar telomere length observed within the most differentiated CD8(+) and CD4(+) T cell subsets. Overall, our data suggest that long-term immune reconstitution was successfully achieved after haploidentical HSCT, a process that appears to have largely relied on de novo T cell production. CI - Copyright (c) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. FAU - Azevedo, Rita I AU - Azevedo RI AD - Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. FAU - Soares, Maria V D AU - Soares MV FAU - Albuquerque, Adriana S AU - Albuquerque AS FAU - Tendeiro, Rita AU - Tendeiro R FAU - Soares, Rui S AU - Soares RS FAU - Martins, Miguel AU - Martins M FAU - Ligeiro, Dario AU - Ligeiro D FAU - Victorino, Rui M M AU - Victorino RM FAU - Lacerda, Joao F AU - Lacerda JF FAU - Sousa, Ana E AU - Sousa AE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130208 PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - 0 (HLA Antigens) SB - IM MH - Adult MH - Anemia, Aplastic/immunology/surgery MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cross-Sectional Studies MH - Female MH - HLA Antigens/*immunology MH - Haploidy MH - Hematopoietic Stem Cell Transplantation/*methods MH - Humans MH - Immunologic Memory MH - Leukemia/immunology/surgery MH - Male MH - Middle Aged MH - T-Lymphocyte Subsets/*immunology MH - Tissue Donors MH - Transplantation Immunology MH - Transplantation, Homologous MH - Young Adult EDAT- 2013/02/12 06:00 MHDA- 2014/03/15 06:00 CRDT- 2013/02/12 06:00 PHST- 2012/10/12 00:00 [received] PHST- 2013/01/19 00:00 [accepted] PHST- 2013/02/12 06:00 [entrez] PHST- 2013/02/12 06:00 [pubmed] PHST- 2014/03/15 06:00 [medline] AID - S1083-8791(13)00053-0 [pii] AID - 10.1016/j.bbmt.2013.01.017 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2013 May;19(5):703-12. doi: 10.1016/j.bbmt.2013.01.017. Epub 2013 Feb 8.