Abstract
We have examined the reconstitution of γδ T cell repertoire diversity after human allogeneic hematopoietic cell transplantation using a polymerase chain reaction (PCR)-based complementarity-determining region (CDR) 3 size spectratyping and DNA sequencing. The CDR3 complexity in the variable region of the T cell receptor (TCR)-δ chain was different amongst the individuals studied. Furthermore, CDR3 size distribution patterns of allogeneic hematopoietic cell transplant recipients were almost completely recovered by a few months after transplantation. In some patients, clonal predominance of the TCRDV1+ T cells became evident during the period after transplantation. In one particular donor/recipient pair, clonal predominance of TCRDV1+ T cells was already present in blood lymphocytes of the donor, and was also observed in the recipient after transplantation. Using this donor/recipient pair, we have questioned whether γδ T cell regeneration occurs via the peripheral expansion of mature T cells in the graft. In the donor lymphocytes, two expanding γδ T cell clones, which were demonstrated by CDR3 sequences of the TCR-δ chain, were recognized. These two clones were identified in the T cells from the recipient post transplant, but not before transplantation. One of the two clones was still detectable 1½ years after the transplant procedure. These results strongly suggest that peripheral expansion of mature T cells in the graft is the principal pathway of γδ T cell regeneration after allogeneic hematopoietic cell transplantation in adults. Bone Marrow Transplantation (2000) 26, 177–185.
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References
McVay LD, Carding SR . Extrathymic origin of human γδ T cells during fetal development J Immunol 1996 157: 2873–2882
McVay LD, Jaswal SS, Kennedy C et al. The generation of human γδ T cell repertoires during fetal development J Immunol 1998 160: 5851–5860
Wells FB, Tatsumi Y, Bluestone JA et al. Phenotypic and functional analysis of positive selection in the γδ T cell lineage J Exp Med 1993 177: 1061–1070
Dent AL, Matis LA, Hooshmand F et al. Self-reactive γδ T cells are eliminated in the thymus Nature 1990 343: 714–719
Mackall CL, Hakim FT, Gress RE . T-cell regeneration: all repertoires are not created equal Immunol Today 1997 18: 245–251
Mackall CL, Granger L, Sheard MA et al. T-cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny Blood 1993 82: 2585–2594
Bomberger C, Singh-Jairam M, Rodey G et al. Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors Blood 1998 91: 2588–2600
Gorski J, Yassai M, Zhu X et al. Circulating T cell repertoire complexity in normal individuals and bone marrow recipients analyzed by CDR3 size spectratyping J Immunol 1994 152: 5109–5119
Hirokawa M, Horiuchi T, Kitabayashi A, et al. Delayed recovery of CDR3 complexity of the T cell receptor-β chain in recipients of allogeneic bone marrow transplants who had virus-associated interstitial pneumonia: monitor of T cell function by CDR3 spectratyping J Allergy Clin Immunol (in press)
Davis MM, Bjorkman PJ . T-cell antigen receptor genes and T-cell recognition Nature 1988 334: 395–402
Storb R, Deeg HJ, Whitehead J et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia New Engl J Med 1986 314: 729–735
Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplantation 1974 18: 295–304
Boeckh M, Bowden RA, Goodrich JM et al. Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation Blood 1992 80: 1358–1364
Yau JC, Dimopoulos MA, Huan SD et al. Prophylaxis of cytomegalovirus infection with ganciclovir in allogeneic marrow transplantation Eur J Haematol 1991 47: 371–376
Horiuchi T, Hirokawa M, Satoh K et al. Clonal expansion of γδ-T lymphocytes in an HTLV-I carrier, associated with chronic neutropenia and rheumatoid arthritis Ann Hematol 1999 78: 101–104
Tsuruta Y, Iwagami S, Furue S et al. Detection of human T cell receptor cDNAs (α, β, γ and δ) by ligation of a universal adaptor to variable region J Immunol Meth 1993 161: 7–21
Lum LG . The kinetics of immune reconstitution after human marrow transplantation Blood 1987 69: 369–380
Parkman R, Weinberg K . Immunological reconstitution following hematopoietic stem cell transplantation. In: Thomas ED, Blume KG, Forman SJ (eds) Hematopoietic Cell Transplantation Blackwell Science: Malden 1999 pp704–711
Viale M, Ferrini S, Bacigalupo A . TCR γδ positive lymphocytes after allogeneic bone marrow transplantation Bone Marrow Transplant 1992 10: 249–250
Dechanet J, Merville P, Lim A et al. Implication of γδ T cells in the human immune response to cytomegalovirus J Clin Invest 1999 103: 1437–1449
Dechanet J, Merville P, Berge F et al. Major expansion of γδ T lymphocytes following cytomegalovirus infection in kidney allograft recipients J Infect Dis 1999 179: 1–8
Mombaerts P, Arnoldi J, Russ F et al. Different roles of αβ and γδ T cells in immunity against an intracellular bacterial pathogen Nature 1993 365: 53–56
Ladel CH, Blum C, Dreher A et al. Protective role of γδ T cells and αβ T cells in tuberculosis Eur J Immunol 1995 25: 2877–2881
Hiromatsu K, Yoshikai Y, Matsuzaki G et al. A protective role of γδ T cells in primary infection with Listeria monocytogenes in mice J Exp Med 1992 175: 49–56
Lamb LS Jr, Henslee-Downey PJ, Parrish RS et al. Increased frequency of TCR γδ+ T cells in disease-free survivors following T cell-depleted, partially mismatched, related donor bone marrow transplantation for leukemia J Hematother 1996 5: 503–509
Pfeffer K, Schoel B, Gulle H et al. Primary responses of human T cells to mycobacteria: a frequent set of γδ+ T cells are stimulated by protease-resistant ligands Eur J Immunol 1990 20: 1175–1179
Tanaka Y, Sano S, Nieves E et al. Nonpeptide ligands for human γδ T cells Proc Natl Acad Sci USA 1994 91: 8175–8179
Constant P, Davodeau F, Peyrat MA et al. Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands Science 1994 264: 267–270
Schild H, Mavaddat N, Litzenberger C et al. The nature of major histocompatibility complex recognition by γδ T cells Cell 1994 76: 29–37
Weitraub BC, Jackson MR, Hedrick SM . γδ T cells can recognize nonclassical MHC in the absence of conventional antigenic peptides J Immunol 1994 153: 3051–3058
Zaia JA . Infections. In: Blume KG, Petz LD (eds) Clinical Bone Marrow Transplantation Churchill Livingstone: New York 1983 pp131–176
Navari RM, Sullivan KM, Springmeyer SC et al. Mycobacterial infections in marrow transplant patients Transplantation 1983 36: 509–513
Aljurf M, Gyger M, Alrajhi A et al. Mycobacterium tuberculosis infection in allogeneic bone marrow transplantation patients Bone Marrow Transplant 1999 24: 551–554
Chang J, Powles R, Mehta J et al. Listeriosis in bone marrow transplant recipients: incidence, clinical features, and treatment Clin Infect Dis 1995 21: 1289–1290
Rocha B, Vassalli P, Guy-Grand D . The extrathymic T-cell development pathway Immunol Today 1992 13: 449–454
Sato K, Ohtsuka K, Hasegawa K et al. Evidence for extrathymic generation of intermediate T cell receptor cells in the liver revealed in thymectomized, irradiated mice subjected to bone marrow transplantation J Exp Med 1995 182: 759–767
Dejbakhsh-Jones S, Jerabek L, Weissman IL, Strober S . Extrathymic maturation of αβ T cells from hemopoietic stem cells J Immunol 1995 155: 3338–3344
Bell EB, Sparhott SM, Drayson MT, Ford WL . The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells J Immunol 1987 139: 1379–1384
Rocha BB . Population kinetics of precursors of IL-2-producing peripheral T lymphocytes: evidence for short life expectancy, continuous renewal, and post-thymic expansion J Immunol 1987 139: 365–372
Rocha B, Dautigny N, Pereira P . Peripheral T lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo Eur J Immunol 1989 19: 905–911
Tanchot C, Rocha B . The organization of mature T-cell pools Immunol Today 1998 19: 575–579
Kisielow P, Miazek A . Positive selection of T cells: rescue from programmed cell death and differentiation require continual engagement of the T cell receptor J Exp Med 1995 181: 1975–1984
Kirberg J, Berns A, von Boehmer H . Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules J Exp Med 1997 186: 1269–1275
Hou S, Hyland L, Ryan KW et al. Virus-specific CD8+ T-cell memory determined by clonal burst size Nature 1994 369: 652–654
Lau LL, Jamieson BD, Somasundaram T, Ahmed R . Cytotoxic T-cell memory without antigen Nature 1994 369: 648–652
Kitabayashi A, Hirokawa M, Horiuchi T et al. Late-onset herpes simplex virus-associated interstitial pneumonia after allogeneic bone marrow transplantation Bone Marrow Transplant 2000 25: 225–226
Acknowledgements
We are grateful to the hematology staff at Akita University Medical Center for their treatment of the patients included in this study. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan (Grant No. 08670508, 10670932), the Yamashita Taro-Kensho Memorial Foundation and the Uehara Memorial Foundation.
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Hirokawa, M., Horiuchi, T., Kawabata, Y. et al. Reconstitution of γδ T cell repertoire diversity after human allogeneic hematopoietic cell transplantation and the role of peripheral expansion of mature T cell population in the graft. Bone Marrow Transplant 26, 177–185 (2000). https://doi.org/10.1038/sj.bmt.1702478
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DOI: https://doi.org/10.1038/sj.bmt.1702478
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