Abstract
Adoptive transfer of mature T cells (ATMTC) through bone marrow (BM) transplantation, first attempted over 20 years ago, has recently emerged as a successful therapy for complete 22q deletion syndrome (22qDS). This provides a potential option to thymic transplantation (TT) for immune reconstitution in 22qDS. Compared to thymic transplant, ATMTC is an easier procedure to accomplish and is available at more centers. However, there are differences in the nature of the T-cell reconstitution that results. Predictably, more naïve T cells and recent thymic emigrants are present in patients treated with thymus transplant. There are no significant differences in mortality between the two procedures, but the number of patients is too limited to conclude that the procedures are equally effective. Adoptive transfer should be pursued as a reasonable treatment for 22qDS patients requiring immune reconstitution when thymus transplant is not available.
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Sullivan K. The clinical, immunological and molecular spectrum of chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Curr Opin Allergy Clin Immunol. 2004;4:505–12.
Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, et al. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood. 2004;104:2574–81.
Rice H, Skinner M, Mahaffey K, Oldham R, Ing L, Hale M, et al. Thymic transplantation for complete DiGeorge syndrome: medical and surgical considerations. J Pediatr Surg. 2004;39:1607–15.
Markert ML, Boeck A, Hale L, Kloster AL, McLaughlin TM, Batchvarova MN. Transplantation of thymus tissue in complete DiGeorge syndrome. New Engl J Med. 1999;341:1180–9.
Markert ML, Sarzotti M, Ozake DA, Sempowski GD, Rhein ME, Hale LP. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003;102:1121–30.
Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, et al. Review of 54 patients with compete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109:4539–47.
Chinn IK, Devlin BH, Li Y, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2007;126:277–81.
Ku CC, Murakami M, Sakamoto A, Kappler J, Marrack P. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science. 2000;288:675–8.
Tan JT, et al. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci USA. 2001;98:8732–7.
Schluns KS, Kieper WC, Jameson SC, Lefrancois L. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol. 2000;1:426–32.
Goldrath AW, et al. Cytokine requirements for acute and basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med. 2002;195:1515–22.
Seddon B, Tomlinson P, Zamoyska R. Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat Immunol. 2003;4:680–6.
Alves NL, Hooibrink B, Arosa FA, van Lier RA. IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro. Blood. 2003;102:2541–6.
Tan JT, et al. Interleukin (IL)–15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med. 2002;195:1523–32.
Land MH, Garcia-Lloret MI, Borzy MS, Rao PN, Aziz N, McGhee SA. Long-term results of bone marrow transplantation in complete DiGeorge syndrome. J Allergy Clin Immunol. 2007;120:908–15.
Daguindau N, Decot V, Nzietchueng R, Ferrand C, Picard C, Latger-Cannard V, et al. Immune constitution monitoring after PBMC transplantation in complete DiGeorge syndrome: an eight-year follow-up. Clin Immunol. 2008;128:164–71.
Goldsobel A, Haas A, Steihm E. Bone marrow transplantation in DiGeorge syndrome. J Pediatr. 1987;111:40–4.
Borzy M, Ridgway D, Noya F, Shearer W. Successful bone marrow transplantation with split lymphoid chimerism in DiGeorge syndrome. J Clin Immunol. 1989;9:386–92.
Matsumoto T, Anamoto N, Kondoh T, Nakayama M, Takayanagi T, Tsuji Y. Complete-type DiGeorge syndrome treated by bone marrow transplantation. Bone Marrow Transplant. 1998;22:927–30.
Bensoussan D, Le Deist F, Latger-Cannard V, Gergoire M, Avinens O, Feugier P, et al. T-cell immune constitution after peripheral blood mononuclear cell transplantation in complete DiGeorge syndrome. Br J Haematol. 2002;117:899–906.
Ohtsuka Y, Shimizu T, Nishizawa K, Ohtaki R, Someya T, Noguchi A, et al. Successful engraftment and decrease of cytomegalovirus load after cord blood stem cell transplantation in a patient with DiGeorge syndrome. Eur J Pediatr. 2004;163:747–8.
Hoenig M, Schulz A, Schuetz C, Debatin K, Friedrich W. Treatment of complete DiGeorge syndrome by repeat transfusions of blood lymphocytes from an HLA-identical sibling donor. Poster presentation 486, American Society of Hematology 46th Annual Meeting, December 4, 2004; San Diego, CA.
Al-Tamemi S, Mazer B, Mitchell D, Albuquerque P, Duncan A, McCusker C, et al. Complete DiGeorge anomaly in the absence of neonatal hypocalcemia and velofacial and cardiac defects. Pediatrics. 2005;116:e457–60.
Janda A, Sedlacek P, Mejstrikova E, Zdrahalova K, Hrusak O, Kalina T, et al. Unrelated partially matched lymphocyte infusions in a patient with complete DiGeorge/CHARGE syndrome. Pediatr Transplant. 2007;11:441–7.
Markert ML. Treatment of infants with complete DiGeorge anomaly. J Allergy Clin Immunol. 2008;121:1063.
Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, et al. Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases. J Allergy Clin Immunol. 2004;113:734–41.
Gennery AR, Barge D, O’Sullivan JJ, Flood TJ, Abinun M, Cant AJ. Antibody deficiency and autoimmunity in 22q112 deletion syndrome. Arch Dis Child. 2002;86:422–5.
Davies JK, Telfer P, Cavenagh JD, Foot N, Neat M. Autoimmune cytopenias in the 22q11.2 deletion syndrome. Clin Lab Haematol. 2003;25:195–7.
Bale PM, Sotelo-Avila C. Maldescent of the thymus: 34 necropsy and 10 surgical cases, including 7 thymuses medial to the mandible. Pediatr Pathol. 1993;13:181–90.
Wilson DI, Burn J, Scambler P, Goodship J. George syndrome: part of CATCH 22. J Med Genet. 1993;30:852–6.
Jawad AF, McDonald-McGinn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr. 2001;139:715–23.
Piliero LM, Sanford AN, McDonald-McGinn DM, Zackai EH, Sullivan KE. T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q112 deletion syndrome. Blood. 2004;103:1020–5.
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McGhee, S.A., Lloret, M.G. & Stiehm, E.R. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol Res 45, 37–45 (2009). https://doi.org/10.1007/s12026-009-8108-7
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DOI: https://doi.org/10.1007/s12026-009-8108-7