title: CD4+ T cell-depleted lymphocyte infusion impairs neither the recovery of recipient thymus nor the development of transplanted thymus.
abstract: Thymus transplantation, in conjunction with bone marrow transplantation (BMT), has been attracting attention for the treatment of various diseases. Recently, donor lymphocyte infusion (DLI) has been used as a helpful tool for establishing donor chimerism and preventing a relapse of leukemia/lymphoma. However, the effects of DLI on transplanted and recipient thymuses have not been explored. We therefore performed DLI in the intrabone marrow-BMT + thymus transplantation setting. We have found that DLI leads to derangements in both recipient thymuses and transplanted thymuses; by 2 wk after BMT, we saw a decrease in total cell number, a lower percentage of CD4(+)CD8(+) cells, and the obliteration of the thymic corticomedullary junction. Four weeks later, the thymic impairment became more serious. However, when we depleted the CD4(+) T cells (CD4(-)-DLI), the recipient thymic recovery and transplanted thymic development were significantly restored by the treatment. In addition, there were much greater levels of TNF-α and Fas ligand, and a lower percentage of regulatory T cells in the DLI group than in the CD4(-)-DLI group. These findings indicate that inflammation induced by DLI, especially by CD4(+) T cells, plays a crucial role in the thymic impairment.
authors: Department of Stem Cell Disorders, Kansai Medical University, 570-8506 Osaka, Japan.
authors: Ming
authors: M
authors: Shi
authors: Ming
authors: M
authors: Li
authors: Yunze
authors: Y
authors: Cui
authors: Lin
authors: L
authors: Liu
authors: Yasushi
authors: Y
authors: Adachi
authors: Susumu
authors: S
authors: Ikehara
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation / Q000379:methods / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000473:pathology / Q000637:transplantation*; D002454:Cell Differentiation / Q000276:immunology*; D007262:Infusions, Intravenous; D008212:Lymphocyte Depletion / Q000009:adverse effects / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020127:Recovery of Function; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*
references: Expert Rev Clin Immunol. 2011 Mar;7(2):205-11
references: 21426258
references: Blood. 2011 Aug 18;118(7):1962-70
references: 21659540
references: Ann N Y Acad Sci. 2009 Sep;1173:774-80
references: 19758228
references: Stem Cells. 2008 Sep;26(9):2211-6
references: 18599811
references: J Clin Invest. 2010 Jan;120(1):343-56
references: 19955659
references: Best Pract Res Clin Haematol. 2011 Sep;24(3):477-83
references: 21925101
references: Bone Marrow Transplant. 2008 Nov;42(9):569-79
references: 18711351
references: N Engl J Med. 1995 Jan 19;332(3):143-9
references: 7800006
references: Best Pract Res Clin Haematol. 2008 Jun;21(2):205-22
references: 18503987
references: Blood. 1998 Nov 15;92(10):3505-14
references: 9808541
references: Lancet. 2009 May 2;373(9674):1550-61
references: 19282026
references: J Clin Invest. 2002 May;109(10):1335-44
references: 12021249
references: Clin Exp Immunol. 2007 Mar;147(3):555-63
references: 17302907
references: Transplantation. 2009 Feb 15;87(3):309-16
references: 19202432
references: Stem Cells Dev. 2011 May;20(5):759-68
references: 20954841
references: Blood. 1998 Jun 1;91(11):4051-5
references: 9596649
references: Blood. 1996 Aug 15;88(4):1501-8
references: 8695872
references: Br J Haematol. 1999 Mar;104(4):795-800
references: 10192442
references: Stem Cells Dev. 2011 Apr;20(4):599-607
references: 20672991
references: Blood. 2002 Jun 1;99(11):4234-6
references: 12010834
references: Semin Immunopathol. 2008 Dec;30(4):439-56
references: 18974988
references: Bone Marrow Transplant. 2006 Jun;37(11):1061-3
references: 16633360
references: Blood. 2010 Jul 1;115(26):5401-11
references: 20354171
references: Blood. 2007 May 1;109(9):4080-8
references: 17213290
references: Nat Med. 2002 Jun;8(6):575-81
references: 12042807
references: Stem Cells. 2005 Mar;23(3):365-70
references: 15749931
references: Blood. 2001 May 1;97(9):2886-95
references: 11313285
references: Blood. 2001 May 15;97(10):3292-9
references: 11342461
references: Biol Blood Marrow Transplant. 1995 Nov;1(1):18-23
references: 9118285
references: Bone Marrow Transplant. 2008 Apr;41(7):659-66
references: 18176618
references: Best Pract Res Clin Haematol. 2008 Jun;21(2):119-28
references: 18503980
references: Ann Med. 1996 Apr;28(2):115-9
references: 8732639
references: Stem Cells. 2007 May;25(5):1186-94
references: 17322105
references: J Autoimmun. 2010 Dec;35(4):414-23
references: 20884174
references: Stem Cells. 2007 Feb;25(2):385-91
references: 17284650
references: Blood. 2007 May 15;109(10):4539-47
references: 17284531