Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation

PLoS ONE

Volumn 7, Issue 5, 2012, Pages

  Albuquerque, Adriana S ^a   Marques, José G ^a,b   Silva, Susana L ^a,b   Ligeiro, Dario ^c   Devlin, Blythe H ^d   Dutrieux, Jacques ^e,f,i   Cheynier, Rémi ^e,f,g,i   Pignata, Claudio ^h   Victorino, Rui M M ^a,b   Markert, M Louise ^d   Sousa, Ana E ^a  

^a INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

^b HOSPITAL DE SANTA MARIA   (Portugal)

^c Ministerio da Saude Portuguese   (Portugal)

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

^e INSTITUT COCHIN   (France)

^f INSERM   (France)

^g UNIVERSITÉ PARIS DESCARTES   (France)

^h UNIVERSITY OF NAPLES FEDERICO II   (Italy)

ⁱ CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; FORKHEAD TRANSCRIPTION FACTOR; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; T LYMPHOCYTE RECEPTOR BETA CHAIN; TRANSCRIPTION FACTOR FOXN1; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; FOXP3 PROTEIN, HUMAN; WHN PROTEIN;

ALLOGRAFT; ALOPECIA; ARTICLE; CASE REPORT; CD4 CD8 RATIO; CELL ACTIVITY; CELL COMPARTMENTALIZATION; CELL COUNT; CELL CYCLE; CELL DIVISION; CELL EXPANSION; CELL MATURATION; CELL SELECTION; DISEASE ASSOCIATION; EXPLANT; FEMALE; HLA MATCHING; HUMAN; HUMAN CELL; INFANT; INVOLUTION; MUTATIONAL ANALYSIS; NUCLEOTIDE SEQUENCE; PRE T LYMPHOCYTE; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN MODIFICATION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; THYMUS APLASIA; THYMUS TRANSPLANTATION; ALLOTRANSPLANTATION; CLINICAL TRIAL; GENETICS; METABOLISM; MISSENSE MUTATION; THYMOCYTE; THYMUS; TRANSPLANTATION;

ALOPECIA; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; INFANT; MUTATION, MISSENSE; THYMOCYTES; THYMUS GLAND; TRANSPLANTATION, HOMOLOGOUS;

EID: 84861013040     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0037042     Document Type: Article

References (45)

1. Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T, (1994) New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372: 103-107.
2. Blackburn CC, Augustine CL, Li R, Harvey RP, Malin MA, et al. (1996) The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc Natl Acad Sci U S A 93: 5742-5746.
3. Chen L, Xiao S, Manley NR, (2009) Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood 113: 567-574.
4. Corbeaux T, Hess I, Swann JB, Kanzler B, Haas-Assenbaum A, et al. (2010) Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc Natl Acad Sci U S A 107: 16613-16618.
5. Zook EC, Krishack PA, Zhang S, Zeleznik-Le NJ, Firulli AB, et al. (2011) Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood 118: 5723-5731.
6. Flanagan SP, (1966) 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res 8: 295-309.
7. Frank J, Pignata C, Panteleyev AA, Prowse DM, Baden H, et al. (1999) Exposing the human nude phenotype. Nature 398: 473-474.
8. Pignata C, Fiore M, Guzzetta V, Castaldo A, Sebastio G, et al. (1996) Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs. Am J Med Genet 65: 167-170.
9. Pignata C, Gaetaniello L, Masci AM, Frank J, Christiano A, et al. (2001) Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation. Blood 97: 880-885.
10. Adriani M, Martinez-Mir A, Fusco F, Busiello R, Frank J, et al. (2004) Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population. Ann Hum Genet 68: 265-268.
11. Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, et al. (2011) First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood 117: 688-696.
12. Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, et al. (2007) Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood 109: 4539-4547.
13. Markert ML, Devlin BH, Chinn IK, McCarthy EA, Li YJ, (2008) Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant 8: 1729-1736.
14. Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, et al. (2004) Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood 104: 2574-2581.
15. Nunes-Cabaco H, Ribot JC, Caramalho I, Serra-Caetano A, Silva-Santos B, et al. (2010) Foxp3 induction in human and murine thymus precedes the CD4(+) CD8(+) stage but requires early T-cell receptor expression. Immunol Cell Biol 88: 523-528.
16. Foxall RB, Soares RS, Albuquerque AS, Cortesao CS, Victorino RM, et al. (2008) Increased frequency of CD25dimCD4+ T-cells in HIV-2 infection, a naturally occurring attenuated form of HIV-1. Clin Immunol 127: 158-167.
17. Azevedo RI, Soares MV, Barata JT, Tendeiro R, Serra-Caetano A, et al. (2009) IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner. Blood 113: 2999-3007.
18. Puisieux I, Even J, Pannetier C, Jotereau F, Favrot M, et al. (1994) Oligoclonality of tumor-infiltrating lymphocytes from human melanomas. J Immunol 153: 2807-2818.
19. Garderet L, Dulphy N, Douay C, Chalumeau N, Schaeffer V, et al. (1998) The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. Blood 91: 340-346.
20. Dion ML, Poulin JF, Bordi R, Sylvestre M, Corsini R, et al. (2004) HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity 21: 757-768.
21. Dion ML, Sekaly RP, Cheynier R, (2007) Estimating thymic function through quantification of T-cell receptor excision circles. Methods Mol Biol 380: 197-213.
22. Fontenot JD, Gavin MA, Rudensky AY, (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4: 330-336.
23. Hori S, Nomura T, Sakaguchi S, (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061.
24. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, et al. (2009) Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30: 899-911.
25. Nunes-Cabaco H, Caramalho I, Sepulveda N, Sousa AE, (2011) Differentiation of human thymic regulatory T cells at the double positive stage. Eur J Immunol 41: 3604-3614.
26. Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, et al. (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 112: 1437-1443.
27. Morrhaye G, Kermani H, Legros JJ, Baron F, Beguin Y, et al. (2009) Impact of growth hormone (GH) deficiency and GH replacement upon thymus function in adult patients. PLoS One 4: e5668.
28. Dulude G, Cheynier R, Gauchat D, Abdallah A, Kettaf N, et al. (2008) The magnitude of thymic output is genetically determined through controlled intrathymic precursor T cell proliferation. J Immunol 181: 7818-7824.
29. Nehls M, Kyewski B, Messerle M, Waldschutz R, Schuddekopf K, et al. (1996) Two genetically separable steps in the differentiation of thymic epithelium. Science 272: 886-889.
30. Ikehara S, Pahwa RN, Fernandes G, Hansen CT, Good RA, (1984) Functional T cells in athymic nude mice. Proc Natl Acad Sci U S A 81: 886-888.
31. Guy-Grand D, Azogui O, Celli S, Darche S, Nussenzweig MC, et al. (2003) Extrathymic T cell lymphopoiesis: ontogeny and contribution to gut intraepithelial lymphocytes in athymic and euthymic mice. J Exp Med 197: 333-341.
32. Kennedy JD, Pierce CW, Lake JP, (1992) Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice as a function of age. J Immunol 148: 1620-1629.
33. Blais ME, Brochu S, Giroux M, Belanger MP, Dulude G, et al. (2008) Why T cells of thymic versus extrathymic origin are functionally different. J Immunol 180: 2299-2312.
34. Schorpp M, Hofmann M, Dear TN, Boehm T, (1997) Characterization of mouse and human nude genes. Immunogenetics 46: 509-515.
35. Schlake T, Schorpp M, Maul-Pavicic A, Malashenko AM, Boehm T, (2000) Forkhead/winged-helix transcription factor Whn regulates hair keratin gene expression: molecular analysis of the nude skin phenotype. Dev Dyn 217: 368-376.
36. Schlake T, (2001) The nude gene and the skin. Exp Dermatol 10: 293-304.
37. Lambolez F, Arcangeli ML, Joret AM, Pasqualetto V, Cordier C, et al. (2006) The thymus exports long-lived fully committed T cell precursors that can colonize primary lymphoid organs. Nat Immunol 7: 76-82.
38. Somech R, Simon AJ, Lev A, Dalal I, Spirer Z, et al. (2009) Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal T cells. J Allergy Clin Immunol 124: 793-800.
39. Poliani PL, Facchetti F, Ravanini M, Gennery AR, Villa A, et al. (2009) Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. Blood 114: 105-108.
40. Cassani B, Poliani PL, Moratto D, Sobacchi C, Marrella V, et al. (2010) Defect of regulatory T cells in patients with Omenn syndrome. J Allergy Clin Immunol 125: 209-216.
41. Kanaya Y, Ohga S, Ikeda K, Furuno K, Ohno T, et al. (2006) Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome. Clin Exp Immunol 144: 85-93.
42. McLean-Tooke A, Barge D, Spickett GP, Gennery AR, (2008) Immunologic defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol 122: 362-367.
43. Bautista JL, Lio CW, Lathrop SK, Forbush K, Liang Y, et al. (2009) Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat Immunol 10: 610-617.
44. Leung MW, Shen S, Lafaille JJ, (2009) TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes. J Exp Med 206: 2121-2130.
45. Bristeau-Leprince A, Mateo V, Lim A, Magerus-Chatinet A, Solary E, et al. (2008) Human TCR alpha/beta+ CD4-CD8- double-negative T cells in patients with autoimmune lymphoproliferative syndrome express restricted Vbeta TCR diversity and are clonally related to CD8+ T cells. J Immunol 181: 440-448.