Abstract
The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided heterogeneous results. In this paper we have undertaken molecular, phenotypic and functional studies aimed at identifying the presence of fully competent T lymphocytes in samples of fetal livers and cord blood. We found mature VDJ TCR β chain transcripts in fetal liver cells taken from 7 to 16 weeks of gestation and a similar pattern was detected in cord blood cells sampled from 13.5 to 20.5 weeks of gestation. A Vβ8 gene sequence comparable to that detected in adult PBMC was found in fetal liver samples at 9 or 17 weeks gestation. PreTα message was detected in all samples and its expression decreased in fetal blood samples with increasing gestational age while Cα message appeared at 9.4 weeks and its expression increased during gestational age. T cell clones obtained from fetal liver cells showed a mature TCR αβ+, CD8+ phenotype and displayed strong alloreactivity against allo-MHC class I molecules. The presence of alloreactive T lymphocytes may explain the failure to engraft in fetuses older than 13 to 16 weeks and may provide insights into fetal liver transplantation. Bone Marrow Transplantation (2000) 25, 135–141.
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References
Touraine JL . Transplantation of fetal hematopoietic lymphopoietic cells in humans, with special reference to in utero transplantation. In: Edwards RG (ed) Fetal Tissue Transplants in Medicine Cambridge 1992 pp 115–122
Takeyama Y, Uehara S, Okamura K, Yajima A . In utero transplantion of fetal hematopoietic cells in the mouse: the effect of donor and recipient gestational maturity Taoku J Exp Med 1997 183: 113–115
Westgren M, Ek S, Bui T et al. Tissue distribution of transplanted fetal liver cells in the human fetal recipient Am J Obstet Gynecol 1997 176: 49–53
Pawliuk R, Eaves C, Humpries RK . Evidence of both ontogeny and transplant dose-regulated expansion of hematopoietic stem cells in vivo Blood 1996 88: 2852–2854
Zanjani ED, Ascensao JL, Flake AW et al. The fetus as an optimal donor and recipient of hemopoietic stem cells Bone Marrow Transplant 1992 10: 107–110
Ringden O, Westgren M, Eik-Nes S et al. Intrauterine transplantation of fetal hematopoietic stem cells to four fetuses with haemoglobinopathies. In: Gluckman E, Coulombel I (eds) Ontogeny of Haematopoietic Aplastic Anemia Colloque Inserm/John Libbey Eurotext, 1995 235: 163–168
Orlandi F, Giambona A, Messana F et al. Evidence of induced non-tolerance in HLA-identical twins with hemoglobinopathy after in utero fetal transplantation Bone Marrow Transplant 1996 18: 637–639
Westgren M, Rindgen O, Eik-Nes S et al. Lack of evidence of permanent engraftment after in utero stem cell transplantation in congenital hemoglobinopathies Transplantation 1996 61: 1176–1179
Touraine JL, Raudrant D, Royo C et al. In utero transplantation of stem cells in the Bare lymphocyte syndrome Lancet 1989 1: 1382
Gaines BA, Colson YL, Kaufman CL, Ildstad S . Facilitating cells enable engraftment of purified fetal liver stem cells in allogeneic recipients Exp Hematol 1996 24: 902
Gale RT . Development of the immune system in human fetal liver Thymus 1987 10: 45–56
Barton FH, Heinly CS . Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment J Exp Med 1995 181: 1445–1458
Tsuda S, Ricke S, Hashimoto Y et al. IL-7 supports D–J but not V–D–J rearrangement of TCR-β gene in fetal liver progenitor cells J Immunol 1996 156: 3223–3242
Strominger JL . Developmental biology of the T cell receptor Science 1989 244: 943–950
Haines BF . The human thymic microenvironment Imm Adv Immunol 1984 36: 87–91
Sanchez MJ, Gutierrez-Amos JC, Fernandez E et al. Putative prethymic T cell precursors within the early human embrionic liver: a molecular and functional analysis J Exp Med 1993 177: 19–33
Aguila HL, Akashi K, Domen J et al. From stem cells to lymphocytes: biology and transplantation Immunol Rev 1997 157: 13–15
Westgren M, Ek S, Bui TH et al. Establishment of a tissue bank for fetal stem cell transplantation Acta Obstet Gynecol Scand 1994 73: 385–387
Di Trapani F, Marino M, D'Alcamo E et al. Prenatal diagnosis of hemoglobin disorders by cordocenthesis at 12 weeks of gestation Prenat Diagn 1991 11: 899–901
Munson JL, Van Twuyer E, Mooijart PDJ et al. Missing T cell receptor Vβ families following blood transfusion. The role of HLA in development of immunization and tolerance Hum Immunol 1995 42: 43–53
Choi Y, Kotzin B, Herron L et al. Interaction of staphylococcus aureus toxin superantigen with human T cells Proc Natl Acad Sci USA 1989 86: 8941–8944
Tanaka J, Imamura M, Kasai M et al. Cytokine gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation Br J Haematol 1991 85: 558–565
Gèneveè C, Diu A, Niorat L et al. An experimentally validated panel of subfamily-specific oligonucleotide primers (Vα1-w29/Vβ1-w24) for the study of human T cell receptor variable V gene segment usage by polimerase chain reaction Eur J Immunol 1992 22: 1261–1269
Rodewald HR, Kretzschmar K, Takeda S et al. Identification of prothymocytes in murine fetal blood T lineage commitment can precede thymus colonization EMBO J 1994 13: 4229–4240
Wang TG, Lybarger L, Soloff R et al. Prethymic transcription of TCR genes by adult murine bone marrow cells Mol Immunol 1996 33: 957–959
Jordan F, McWhinnie AJ, Turner S et al. Comparison of HLA-DRβ1 typing by DNA-RFLP, PCR-SSO and PCR-SSP methods and their application in providing matched unrelated donors for bone marrow transplantation Tissue Antigens 1995 45: 103–110
Barbey C, Irion O, Helg C et al. Characterization of the cytotoxic alloresponse of cord blood Bone Marrow Transplant 1998 22: 26–30
Acknowledgements
We are grateful to Associazione per la Ricerca ‘Piera Cutino’ for his continuous support and to Prof A Lanzavecchia of Basel Institute for Immunology for criticism of our work. This work was supported in part by: CNR project No. 95.04689.ST75, Assessorato Sanità Regione Sicilia project No. T5/12–1995; CEE project POP 90/93.
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Renda, M., Fecarotta, E., Dieli, F. et al. Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation. Bone Marrow Transplant 25, 135–141 (2000). https://doi.org/10.1038/sj.bmt.1702108
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DOI: https://doi.org/10.1038/sj.bmt.1702108
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