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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Chimerism


High impact information on Chimerism

  • These findings indicate a crucial role for donor T cells in host Langerhans cell replacement, and show that host dendritic cells can persist in nonlymphoid tissue for the duration of an animal's life and can trigger GVHD despite complete blood chimerism [6].
  • To study the relevance of the resulting microchimerism for allograft acceptance, we analyzed a rat model of cyclosporine-induced tolerance for strongly incompatible heart allografts [7].
  • Lasting mixed chimerism was achieved in KO mice by cotransplantation of GalT KO and WT marrow after lethal irradiation [8].
  • B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease [9].
  • Surprisingly, although low numbers of Nf1-deficient cells consistently outcompeted wild-type cells, levels of chimerism were stable over months of observation, and MPD was not observed unless threshold numbers of mutant cells were injected [10].

Chemical compound and disease context of Chimerism


Biological context of Chimerism


Anatomical context of Chimerism

  • Three principal approaches are being evaluated: hematopoietic chimerism, lymphocyte depletion and costimulation blockade [21].
  • These include newer and safer protocols to create hematopoietic chimerism, the development of more-powerful T cell depleting antibodies, the identification of additional costimlulatory pathways as molecular targets and the identification of a role for suppressor cells in transplant tolerance [22].
  • Although recipients of perforin-deficient or normal allogeneic T cells exhibited hematopoietic engraftment exclusively of donor origin, recipients of FasL-defective donor T cells exhibited significant mixed chimerism (Ly-5.1/Ly-5.2) [23].
  • We investigated lineage-specific chimerism in 15 patients receiving an allogeneic peripheral blood stem cell (PBSC) transplant from an HLA-identical (n = 14) or a 5/6 antigen-matched sibling donor after a preparative regimen of cyclophosphamide and fludarabine [24].
  • Thus, transfer of allogeneic donor T cells may help break functional tolerance of a host immune system to a solid tumor, thereby providing a rationale for the generation of mixed hematopoietic chimerism by NST prior to tumor cell vaccination [25].

Associations of Chimerism with chemical compounds

  • A complete and long-term chimerism was established when donor mice had been induced to develop tolerance of BXSB male antigens by combined treatment with BXSB male spleen cells and cyclophosphamide [26].
  • Whereas anti-CD40L mAb facilitated chimerism, neither sirolimus nor CsA resulted in substantial alloengraftment [27].
  • The results with KL and 5-FU are encouraging for the further refinement of non-TBI, nonbusulfan techniques to achieve stable mixed chimerism [28].
  • Rapamycin (rapa), methylprednisolone (MP), FTY720, and mycophenolate mofetil (MMF), in contrast, have no negative effect on chimerism or tolerance development [29].
  • Our results show that calcineurin inhibitors (cyclosporin A [CyA] or tacrolimus [FK]) inhibit development of long-term chimerism and abrogate tolerance induction in this model [29].

Gene context of Chimerism

  • In Agtr1a -/- <--> +/+ mice, these changes were proportional to the degree of chimerism [30].
  • Overall, microchimerism was found in CD3, CD19, and CD14 subsets in approximately one third of women and in CD56/16 in one half of women [1].
  • In long-term chimerism experiments, IL-10 infusions caused a significant increase in early post-BMT mortality caused by a profound anemia typically associated with graft rejection and aplasia [31].
  • Microchimerism, donor dendritic cells, and alloimmune reactivity in recipients of Flt3 ligand-mobilized hemopoietic cells: modulation by tacrolimus [32].
  • Targeted disruption of T cell costimulatory pathways, particularly CD28 and CD40, has allowed for the development of minimally myeloablative strategies for the induction of mixed allogeneic chimerism and donor-specific tolerance across full MHC barriers [33].

Analytical, diagnostic and therapeutic context of Chimerism


  1. Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Evans, P.C., Lambert, N., Maloney, S., Furst, D.E., Moore, J.M., Nelson, J.L. Blood (1999) [Pubmed]
  2. Chimerism and clinical outcomes of 110 recipients of unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide. Girgis, M., Hallemeier, C., Blum, W., Brown, R., Lin, H.S., Khoury, H., Goodnough, L.T., Vij, R., Devine, S., Wehde, M., Postma, S., Oza, A., Dipersio, J., Adkins, D. Blood (2005) [Pubmed]
  3. Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation. Kapelushnik, J., Or, R., Filon, D., Nagler, A., Cividalli, G., Aker, M., Naparstek, E., Slavin, S., Oppenheim, A. Blood (1995) [Pubmed]
  4. Transplantation of filgrastim-mobilized peripheral blood stem cells from HLA-identical sibling or alternative family donors in patients with hematologic malignancies: a prospective comparison on clinical outcome, immune reconstitution, and hematopoietic chimerism. Beelen, D.W., Ottinger, H.D., Elmaagacli, A., Scheulen, B., Basu, O., Kremens, B., Havers, W., Grosse-Wilde, H., Schaefer, U.W. Blood (1997) [Pubmed]
  5. Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Mapara, M.Y., Kim, Y.M., Wang, S.P., Bronson, R., Sachs, D.H., Sykes, M. Blood (2002) [Pubmed]
  6. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Merad, M., Hoffmann, P., Ranheim, E., Slaymaker, S., Manz, M.G., Lira, S.A., Charo, I., Cook, D.N., Weissman, I.L., Strober, S., Engleman, E.G. Nat. Med. (2004) [Pubmed]
  7. The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat. Ko, S., Deiwick, A., Jäger, M.D., Dinkel, A., Rohde, F., Fischer, R., Tsui, T.Y., Rittmann, K.L., Wonigeit, K., Schlitt, H.J. Nat. Med. (1999) [Pubmed]
  8. Tolerization of anti-Galalpha1-3Gal natural antibody-forming B cells by induction of mixed chimerism. Yang, Y.G., deGoma, E., Ohdan, H., Bracy, J.L., Xu, Y., Iacomini, J., Thall, A.D., Sykes, M. J. Exp. Med. (1998) [Pubmed]
  9. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. Sharabi, Y., Sachs, D.H. J. Exp. Med. (1989) [Pubmed]
  10. Quantitative effects of Nf1 inactivation on in vivo hematopoiesis. Zhang, Y., Taylor, B.R., Shannon, K., Clapp, D.W. J. Clin. Invest. (2001) [Pubmed]
  11. Simultaneous LFA-1 and CD40 ligand antagonism prevents airway remodeling in orthotopic airway transplantation: implications for the role of respiratory epithelium as a modulator of fibrosis. Murakawa, T., Kerklo, M.M., Zamora, M.R., Wei, Y., Gill, R.G., Henson, P.M., Grover, F.L., Nicolls, M.R. J. Immunol. (2005) [Pubmed]
  12. Extended follow-up of patients treated with imatinib mesylate (gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation: durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease. DeAngelo, D.J., Hochberg, E.P., Alyea, E.P., Longtine, J., Lee, S., Galinsky, I., Parekkedon, B., Ritz, J., Antin, J.H., Stone, R.M., Soiffer, R.J. Clin. Cancer Res. (2004) [Pubmed]
  13. Endothelial cell chimerism after renal transplantation in a rat model. Xu, W., Baelde, H.J., Lagaaij, E.L., De Heer, E., Paul, L.C., Bruijn, J.A. Transplantation (2002) [Pubmed]
  14. Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation. Wäsch, R., Reisser, S., Hahn, J., Bertz, H., Engelhardt, M., Kunzmann, R., Veelken, H., Holler, E., Finke, J. Bone Marrow Transplant. (2000) [Pubmed]
  15. Successful allogeneic bone marrow transplantation in juvenile CML: conditioning or graft-versus-leukaemia effect? Rassam, S.M., Katz, F., Chessells, J.M., Morgan, G. Bone Marrow Transplant. (1993) [Pubmed]
  16. A novel target cell for c-fos-induced oncogenesis: development of chondrogenic tumours in embryonic stem cell chimeras. Wang, Z.Q., Grigoriadis, A.E., Möhle-Steinlein, U., Wagner, E.F. EMBO J. (1991) [Pubmed]
  17. The phenotype of lymphoid cells and thymic epithelium correlates with development of autoimmune insulitis in NOD in equilibrium with C57BL/6 allophenic chimeras. Forsgren, S., Dahl, U., Söderström, A., Holmberg, D., Matsunaga, T. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  18. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Falkenburg, J.H., Wafelman, A.R., Joosten, P., Smit, W.M., van Bergen, C.A., Bongaerts, R., Lurvink, E., van der Hoorn, M., Kluck, P., Landegent, J.E., Kluin-Nelemans, H.C., Fibbe, W.E., Willemze, R. Blood (1999) [Pubmed]
  19. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Giaccone, L., McCune, J.S., Maris, M.B., Gooley, T.A., Sandmaier, B.M., Slattery, J.T., Cole, S., Nash, R.A., Storb, R.F., Georges, G.E. Blood (2005) [Pubmed]
  20. Myeloid and lymphoid chimerism after T-cell-depleted bone marrow transplantation: evaluation of conditioning regimens using the polymerase chain reaction to amplify human minisatellite regions of genomic DNA. Mackinnon, S., Barnett, L., Bourhis, J.H., Black, P., Heller, G., O'Reilly, R.J. Blood (1992) [Pubmed]
  21. Knowledge about transplantation tolerance gained in primates. Knechtle, S.J. Curr. Opin. Immunol. (2000) [Pubmed]
  22. Immunotherapy as a means to induce transplantation tolerance. Adler, S.H., Turka, L.A. Curr. Opin. Immunol. (2002) [Pubmed]
  23. Graft-versus-host-disease-associated lymphoid hypoplasia and B cell dysfunction is dependent upon donor T cell-mediated Fas-ligand function, but not perforin function. Baker, M.B., Riley, R.L., Podack, E.R., Levy, R.B. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  24. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Childs, R., Clave, E., Contentin, N., Jayasekera, D., Hensel, N., Leitman, S., Read, E.J., Carter, C., Bahceci, E., Young, N.S., Barrett, A.J. Blood (1999) [Pubmed]
  25. Successful therapy of metastatic cancer using tumor vaccines in mixed allogeneic bone marrow chimeras. Luznik, L., Slansky, J.E., Jalla, S., Borrello, I., Levitsky, H.I., Pardoll, D.M., Fuchs, E.J. Blood (2003) [Pubmed]
  26. Marrow transplantation from tolerant donors to treat and prevent autoimmune diseases in BXSB mice. Himeno, K., Good, R.A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  27. Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions. Taylor, P.A., Lees, C.J., Wilson, J.M., Ehrhardt, M.J., Campbell, M.T., Noelle, R.J., Blazar, B.R. Blood (2002) [Pubmed]
  28. Host conditioning with 5-fluorouracil and kit-ligand to provide for long-term bone marrow engraftment. van Os, R., Dawes, D., Mislow, J.M., Witsell, A., Mauch, P.M. Blood (1997) [Pubmed]
  29. The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade. Blaha, P., Bigenzahn, S., Koporc, Z., Schmid, M., Langer, F., Selzer, E., Bergmeister, H., Wrba, F., Kurtz, J., Kiss, C., Roth, E., Muehlbacher, F., Sykes, M., Wekerle, T. Blood (2003) [Pubmed]
  30. Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A receptor gene. Evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells. Matsusaka, T., Nishimura, H., Utsunomiya, H., Kakuchi, J., Niimura, F., Inagami, T., Fogo, A., Ichikawa, I. J. Clin. Invest. (1996) [Pubmed]
  31. Interleukin-10 administration decreases survival in murine recipients of major histocompatibility complex disparate donor bone marrow grafts. Blazar, B.R., Taylor, P.A., Smith, S., Vallera, D.A. Blood (1995) [Pubmed]
  32. Microchimerism, donor dendritic cells, and alloimmune reactivity in recipients of Flt3 ligand-mobilized hemopoietic cells: modulation by tacrolimus. Morelli, A.E., Antonysamy, M.A., Takayama, T., Hackstein, H., Chen, Z., Qian, S., Zurowski, N.B., Thomson, A.W. J. Immunol. (2000) [Pubmed]
  33. Primary and secondary immunocompetence in mixed allogeneic chimeras. Williams, M.A., Adams, A.B., Walsh, M.B., Shirasugi, N., Onami, T.M., Pearson, T.C., Ahmed, R., Larsen, C.P. J. Immunol. (2003) [Pubmed]
  34. Fetal-maternal microchimerism: impact on hematopoietic stem cell transplantation. Ichinohe, T., Teshima, T., Matsuoka, K., Maruya, E., Saji, H. Curr. Opin. Immunol. (2005) [Pubmed]
  35. Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia. Jurlander, J., Caligiuri, M.A., Ruutu, T., Baer, M.R., Strout, M.P., Oberkircher, A.R., Hoffmann, L., Ball, E.D., Frei-Lahr, D.A., Christiansen, N.P., Block, A.M., Knuutila, S., Herzig, G.P., Bloomfield, C.D. Blood (1996) [Pubmed]
  36. Epithelial tissue chimerism after human hematopoietic cell transplantation is a real phenomenon. Spyridonidis, A., Schmitt-Gräff, A., Tomann, T., Dwenger, A., Follo, M., Behringer, D., Finke, J. Am. J. Pathol. (2004) [Pubmed]
  37. Induction of remission of severe and refractory rheumatoid arthritis by allogeneic mixed chimerism. Burt, R.K., Oyama, Y., Verda, L., Quigley, K., Brush, M., Yaung, K., Statkute, L., Traynor, A., Barr, W.G. Arthritis Rheum. (2004) [Pubmed]
  38. The xenotransplantation of goat and human hematopoietic cells to sheep fetuses. Colas, G., Hollands, P., Locatelli, A., Le Vern, Y., Cotinot, C., Canepa, S., Kerboeuf, D., Thomas, A., Pisselet, C., Dacheux, J.L., Popescu, P., Salmon, H. Transplantation (1999) [Pubmed]
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