Bone Marrow T Cells are Superior to Splenic T Cells to Induce Chimeric Conversion After Non-Myeloablative Bone Marrow Transplantation
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells. Methods: Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21. Results: When the same dose of T cells, 5-10×105 (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graftversus- host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine. Conclusions: Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.
Abstract
Background/Aims: The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells. Methods: Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21. Results: When the same dose of T cells, 5-10×105 (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graftversus- host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine. Conclusions: Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.
참고문헌 (37)
- Weiden PL, "Antileukemic effect of graft-versus-host disease in human recipients of allogeneicmarrow grafts", N Engl J Med, 300, pp.1068~1073 (1979)
- Horowitz MM, "Graft-versus-leukemia reactions after bone marrow transplantation", Blood, 75, pp.555~562 (1990)
- Kolb HJ, "Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients", Blood, 76, pp.2462~2465 (1990)
- Porter DL, "Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia", N Engl J Med, 330, pp.100~106 (1994)
- Drobyski WR, "Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose", Blood, 82, pp.2310~2318 (1993)
- Zeng D, "Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact on allogeneic bone marrow transplantation", Blood, 99, pp.1449~1457 (2002)
- von Andrian UH, "T-cell function and migration : two sides of the same coin", N Engl J Med, 343, pp.1020~1034 (2000)
- Masopust D, "Preferential localization of effector memory cells in nonlymphoid tissue", Science, 291, pp.2413~2417 (2001)
- Feuerer M, "Bone marrow as a priming site for T-cell responses to blood-borne antigen", Nat Med, 9, pp.1151~1157 (2003)
- Mazo IB, "Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells", Immunity, 22, pp.259~270 (2005)
- Parretta E, "CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone marrow", J Immunol, 174, pp.7654~7664 (2005)
- Lan F, "Allogeneic bone marrow cells that facilitate complete chimerism and eliminate tumor cells express both CD8 and T-cell antigen receptoralphabeta", Blood, 97, pp.3458~3465 (2001)
- Sykes M, "Mixed chimerism and transplant tolerance", Immunity, 14, pp.417~424 (2001)
- Baron F, "Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning", Leukemia, 20, pp.1690~1700 (2006)
- Mapara MY, "Donor lymphocyte infusions mediate superior graft-versusleukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells", Blood, 100, pp.1903~1909 (2002)
- Mapara MY, "Donor lymphocyte infusion-mediated graft-versus-leukemia effects in mixed chimeras established with a nonmyeloablative conditioning regimen: extinction of graft-versus-leukemia effects after conversion to full donor chimerism", Transplantation, 76, pp.297~305 (2003)
- Collins RH, Jr, "Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation", J Clin Oncol, 15, pp.433~444 (1997)
- Cho SG, "Anti-NK cell treatment induces stable mixed chimerism in MHC-mismatched, T cell-depleted, nonmyeloablative bone marrow transplantation", Exp Hematol, 32, pp.1246~1254 (2004)
- Cho SG, "Immunoregulatory effects of allogeneic mixed chimerism induced by nonmyeloablative bone marrow transplantation on chronic inflammatory arthritis and autoimmunity in interleukin-1 receptor antagonist-deficient mice", Arthritis Rheum, 54, pp.1878~1887 (2006)
- Cooke KR, "An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. the roles of minor H antigens and endotoxin", Blood, 88, pp.3230~3239 (1996)
- Sykes M, "Unusual T cell populations in adult murine bone marrow: prevalence of CD3+CD4-CD8- and alpha beta TCR+ NK1.1+ cells", J Immunol, 145, pp.3209~3215 (1990)
- Westermann J, "Distribution of lymphocyte subsets and natural killer cells in the human body", Clin Investig, 70, pp.539~544 (1992)
- Zeng D, "Bone marrow NK1.1 (-) and NK1.1 (+) T cells reciprocally regulate acute graft versus host disease", J Exp Med, 189, pp.1073~1081 (1999)
- Liang Y, "Donor CD8+ T cells facilitate induction of chimerism and tolerance without GVHD in autoimmune NOD mice conditioned with anti-CD3 mAb", Blood, 105, pp.2180~2188 (2005)
- Di Rosa F, "Bone marrow CD8 T cells are in a different activation state than those in lymphoid periphery", Eur J Immunol, 32, pp.1873~1880 (2002)
- Avigdor A, "CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem", progenitor cells to bone marrow, 2004, pp.103, 2981~2989
- Anderlini P, "Peripheral blood stem cell donation: an analysis from the International Bone Marrow Transplant Registry (IBMTR) and European Group for Blood and Marrow Transplant (EBMT) databases", Bone Marrow Transplant, 27, pp.689~692 (2001)
- Bensinger WI, "Transplantation of bone marrow as compared with peripheral-blood cells from HLAidentical relatives in patients with hematologic cancers", N Engl J Med, 344, pp.175~181 (2001)
- Eapen M, "Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: the Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry", J Clin Oncol, 22, pp.4872~4880 (2004)
- Schmitz N, "Long-term outcome of patients given transplants of mobilized blood or bone marrow: a report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation", Blood, 108, pp.4288~4290 (2006)
- Schrezenmeier H, "Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia", Blood, 110, pp.1397~1400 (2007)
- Exner BG, "Clinical applications of mixed chimerism", Ann N Y Acad Sci, 872, pp.377~385 (1999)
- Passweg JR, "Tichelli A. Use of natural killer cells in hematopoetic stem cell transplantation", Bone Marrow Transplant, 35, pp.637~643 (2005)
- Passweg JR, "Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation", Leukemia, 18, pp.1835~1838 (2004)
- Martin PJ, "Donor CD8 cells prevent allogeneic marrow graft rejection in mice: potential implications for marrow transplantation in humans", J Exp Med, 178, pp.703~712 (1993)
- Palathumpat V, "The role of purified CD8+ T cells in graft-versus-leukemia activity and engraftment after allogeneic bone marrow transplantation", Transplantation, 60, pp.355~361 (1995)
- Zou L, "Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12", CXCR4 signals, 2004, pp.64, 8451~8455