iNKT Cells: Innate lymphocytes with a diverse response

Critical Reviews in Immunology

Volumn 34, Issue 1, 2014, Pages 81-90

  Monteiro, Marta ^a,b   Graca, Luis ^a,b  

^a INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

^b INSTITUTO GULBENKIAN DE CIÊNCIA   (Portugal)

Author keywords

galactosylcermide; Cytokines; Effector; Foxp3; IL 17; Memory; Na ve; Natural killer T cells; Plasticity; T cell receptor

Indexed keywords

CHEMOKINE; CHEMOKINE RECEPTOR; GAMMA INTERFERON; INTERLEUKIN 17; INTERLEUKIN 4; RETINOIC ACID RECEPTOR GAMMA; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR PLZF; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL LINEAGE; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; HUMAN; INNATE IMMUNITY; LYMPHOCYTE DIFFERENTIATION; NATURAL KILLER T CELL; NONHUMAN; PHENOTYPIC PLASTICITY; PRE T LYMPHOCYTE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH17 CELL; TH2 CELL; THYMOCYTE;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CELL LINEAGE; CYTOKINES; HUMANS; IMMUNITY, INNATE; NATURAL KILLER T-CELLS; RECEPTORS, ANTIGEN, T-CELL; TH1-TH2 BALANCE; THYMUS GLAND;

EID: 84896836127     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevImmunol.2014010088     Document Type: Article

References (88)

1. Gumperz JE, Miyake S, Yamamura T, Brenner MB. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Expl Med. 2002; 195 (5): 625-36.
2. Michel ML, Keller AC, Paget C, Fujio M, Trottein F, Savage PB, Wong CH, Schneider E, Dy M, Leitede-Moraes MC. Identification of an IL-17-producing NK1. 1 (neg) iNKT cell population involved in airway neutrophilia. J Exp Med. 2007; 204 (5): 995-1001.
3. Niemeyer M, Darmoise A, Mollenkopf HJ, Hahnke K, Hurwitz R, Besra GS, Schaible UE, Kaufmann SH. Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses. Immunology. 2008; 123 (1): 45-56.
4. Wen X, Rao P, Carreno LJ, Kim S, Lawrenczyk A, Porcelli SA, Cresswell P, Yuan W. Human CD1d knock-in mouse model demonstrates potent antitumor potential of human CD1d-restricted invariant natural killer T cells. Proc Natl Acad Sci U S A. 2013; 110 (8): 2963-8.
5. Biburger M, Tiegs G. Activation-induced NKT cell hyporesponsiveness protects from alpha-galactosylceramide hepatitis and is independent of active transregulatory factors. J Leukocyte Biol. 2008; 84 (1): 264-79.
6. Lisbonne M, Diem S, de Castro Keller A, Lefort J, Araujo LM, Hachem P, Fourneau JM, Sidobre S, Kronenberg M, Taniguchi M, Van Endert P, Dy M, Askenase P, Russo M, Vargaftig BB, Herbelin A, Leite-de-Moraes MC. Cutting edge: invariant V alpha 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model. J Immunol. 2003; 171 (4): 1637-41.
7. Gober MD, Fishelevich R, Zhao Y, Unutmaz D, Gaspari AA. Human natural killer T cells infiltrate into the skin at elicitation sites of allergic contact dermatitis. J Invest Dermatol. 2008; 128 (6): 1460-9.
8. Mattner J, Savage PB, Leung P, Oertelt SS, Wang V, Trivedi O, Scanlon ST, Pendem K, Teyton L, Hart J, Ridgway WM, Wicker LS, Gershwin ME, Bendelac A. Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe. 2008; 3 (5): 304-15.
9. Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol. 2007; 25: 297-336.
10. Jiang X, Shimaoka T, Kojo S, Harada M, Watarai H, Wakao H, Ohkohchi N, Yonehara S, Taniguchi M, Seino K. Cutting edge: critical role of CXCL16/CXCR6 in NKT cell trafficking in allograft tolerance. J Immunol. 2005; 175 (4): 2051-5.
11. Meyer EH, Goya S, Akbari O, Berry GJ, Savage PB, Kronenberg M, Nakayama T, DeKruyff RH, Umetsu DT. Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc Natl Acad Sci U S A. 2006; 103 (8): 2782-7.
12. Hong S, Wilson MT, Serizawa I, Wu L, Singh N, Naidenko OV, Miura T, Haba T, Scherer DC, Wei J, Kronenberg M, Koezuka Y, Van Kaer L. The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nat Med. 2001; 7 (9): 1052-6.
13. Singh AK, Wilson MT, Hong S, Olivares-Villagomez D, Du C, Stanic AK, Joyce S, Sriram S, Koezuka Y, Van Kaer L. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J Exp Med. 2001; 194 (12): 1801-11.
14. Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005; 6 (8): 810-8.
15. Koch M, Stronge VS, Shepherd D, Gadola SD, Mathew B, Ritter G, Fersht AR, Besra GS, Schmidt RR, Jones EY, Cerundolo V. The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat Immunol. 2005; 6 (8): 819-26.
16. Rossjohn J, Pellicci DG, Patel O, Gapin L, Godfrey DI. Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev Immunol. 2012; 12 (12): 845-57.
17. Dellabona P, Padovan E, Casorati G, Brockhaus M, Lanzavecchia A. An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4-8-T cells. J Exp Med. 1994; 180 (3): 1171-6.
18. Porcelli S, Yockey CE, Brenner MB, Balk SP. Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8-alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain. J Exp Med. 1993; 178 (1): 1-16.
19. Lantz O, Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8-T cells in mice and humans. J Exp Med. 1994; 180 (3): 1097-106.
20. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Koseki H, Taniguchi M. CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science. 1997; 278 (5343): 1626-9.
21. Brossay L, Chioda M, Burdin N, Koezuka Y, Casorati G, Dellabona P, Kronenberg M. CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med. 1998; 188 (8); 1521-8.
22. Benlagha K, Weiss A, Beavis A, Teyton L, Bendelac A. In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. J Exp Med. 2000; 191 (11): 1895-903.
23. Matsuda JL, Naidenko OV, Gapin L, Nakayama T, Taniguchi M, Wang CR, Koezuka Y, Kronenberg M. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med. 2000; 192 (5): 741-54.
24. Rhost S, Sedimbi S, Kadri N, Cardell SL. Immunomodulatory type II natural killer T lymphocytes in health and disease. Scand J Immunol. 2012; 76 (3): 246-55.
25. Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V. Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med. 2004; 199 (7): 947-57.
26. Godfrey DI, Berzins SP. Control points in NKT-cell development. Nat Rev Immunol. 2007; 7 (7): 505-18.
27. Chen H, Huang H, Paul WE. NK1. 1+ CD4+ T cells lose NK1. 1 expression upon in vitro activation. J Immunol. 1997; 158 (11): 5112-9.
28. Crowe NY, Uldrich AP, Kyparissoudis K, Hammond KJ, Hayakawa Y, Sidobre S, Keating R, Kronenberg M, Smyth MJ, Godfrey DI. Glycolipid antigen drives rapid expansion and sustained cytokine production by NK T cells. J Immunol. 2003; 171 (8): 4020-7.
29. Wilson MT, Johansson C, Olivares-Villagomez D, Singh AK, Stanic AK, Wang CR, Joyce S, Wick MJ, Van Kaer L. The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc Natl Acad Sci U S A. 2003; 100 (19): 10913-8.
30. Crowe NY, Coquet JM, Berzins SP, Kyparissoudis K, Keating R, Pellicci DG, Hayakawa Y, Godfrey DI, Smyth MJ. Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med. 2005; 202 (9): 1279-88.
31. Chan AC, Leeansyah E, Cochrane A, d'Udekem d'Acoz Y, Mittag D, Harrison LC, Godfrey DI, Berzins SP. Exvivo analysis of human natural killer T cells demonstrates heterogeneity between tissues and within established CD4 (+) and CD4 (-) subsets. Clin Exp Immunol. 2013; 172 (1): 129-37.
32. Coquet JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA, McKenzie BS, Berzins SP, Smyth MJ, Godfrey DI. Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1. 1-NKT cell population. Proc Natl Acad Sci the U S A. 2008; 105 (32): 11287-92.
33. Monteiro M, Almeida CF, Agua-Doce A, Graca L. Induced IL-17-producing invariant NKT cells require activation in presence of TGF-beta and IL-1beta. J Immunol. 2013; 190 (2): 805-11.
34. Michel ML, Mendes-da-Cruz D, Keller AC, Lochner M, Schneider E, Dy M, Eberl G, Leite-de-Moraes MC. Critical role of ROR-gammat in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. Proc Natl Acad Sci U S A. 2008; 105 (50): 19845-50.
35. Monteiro M, Graca L. Response to comment on "Induced IL-17-producing invariant NKT cells require activation in presence of TGF-beta and IL-1beta". J Immunol. 2013; 190 (12): 5910-1.
36. Gapin L, Matsuda JL, Surh CD, Kronenberg M. NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nat Immunol. 2001; 2 (10): 971-8.
37. Egawa T, Eberl G, Taniuchi I, Benlagha K, Geissmann F, Hennighausen L, Bendelac A, Littman DR. Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors. Immunity. 2005; 22 (6): 705-16.
38. Bezbradica JS, Hill T, Stanic AK, Van Kaer L, Joyce S. Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc Natl Acad Sci U S A. 2005; 102 (14): 5114-9.
39. Bendelac A. Positive selection of mouse NK1+ T cells by CD1-expressing cortical thymocytes. J Exp Med. 1995; 182 (6): 2091-6.
40. McNab FW, Berzins SP, Pellicci DG, Kyparissoudis K, Field K, Smyth MJ, Godfrey DI. The influence of CD1d in postselection NKT cell maturation and homeostasis. J Immunol. 2005; 175 (6): 3762-8.
41. Moran AE, Holzapfel KL, Xing Y, Cunningham NR, Maltzman JS, Punt J, Hogquist KA. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J Exp Med. 2011; 208 (6): 1279-89.
42. Seiler MP, Mathew R, Liszewski MK, Spooner CJ, Barr K, Meng F, Singh H, Bendelac A. Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling. Nat Immunol. 2012; 13 (3): 264-71.
43. Savage AK, Constantinides MG, Han J, Picard D, Martin E, Li B, Lantz O, Bendelac A. The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity. 2008; 29 (3): 391-403.
44. Kovalovsky D, Uche OU, Eladad S, Hobbs RM, Yi W, Alonzo E, Chua K, Eidson M, Kim HJ, Im JS, Pandolfi PP, Sant'Angelo DB. The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nat Immunol. 2008; 9 (9): 1055-64.
45. Kovalovsky D, Alonzo ES, Uche OU, Eidson M, Nichols KE, Sant'Angelo DB. PLZF induces the spontaneous acquisition of memory/effector functions in T cells independently of NKT cell-related signals. J Immunol. 2010; 184 (12): 6746-55.
46. Savage AK, Constantinides MG, Bendelac A. Promyelocytic leukemia zinc finger turns on the effector T cell program without requirement for agonist TCR signaling. J Immunol. 2011; 186 (10): 5801-6.
47. Watarai H, Sekine-Kondo E, Shigeura T, Motomura Y, Yasuda T, Satoh R, Yoshida H, Kubo M, Kawamoto H, Koseki H, Taniguchi M. Development and function of invariant natural killer T cells producing T (h) 2-and T (h) 17-cytokines. PLoS Biol. 2012: 10 (2): e1001255.
48. Constantinides MG, Bendelac A. Transcriptional regulation of the NKT cell lineage. Curr Opin Immunol. 2013; 25 (2): 161-7.
49. Matsuda JL, Zhang Q, Ndonye R, Richardson SK, Howell AR, Gapin L. T-bet concomitantly controls migration, survival, and effector functions during the development of Valpha14i NKT cells. Blood. 2006; 107 (7): 2797-805.
50. Townsend MJ, Weinmann AS, Matsuda JL, Salomon R, Farnham PJ, Biron CA, Gapin L, Glimcher LH. T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. Immunity. 2004; 20 (4): 477-94.
51. Benlagha K, Kyin T, Beavis A, Teyton L, Bendelac A. A thymic precursor to the NK T cell lineage. Science. 2002; 296 (5567): 553-5.
52. Pellicci DG, Hammond KJ, Uldrich AP, Baxter AG, Smyth MJ, Godfrey DI. A natural killer T (NKT) cell developmental pathway iInvolving a thymus-dependent NK1. 1 (-) CD4 (+) CD1d-dependent precursor stage. J Exp Med. 2002; 195 (7): 835-44.
53. Yoshimoto T, Paul WE. CD4pos, NK1. 1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994; 179 (4): 1285-95.
54. Terashima A, Watarai H, Inoue S, Sekine E, Nakagawa R, Hase K, Iwamura C, Nakajima H, Nakayama T, Taniguchi M. A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. J Exp Med. 2008; 205 (12): 2727-33.
55. Guo J, Hawwari A, Li H, Sun Z, Mahanta SK, Littman DR, Krangel MS, He YW. Regulation of the TCRalpha repertoire by the survival window of CD4 (+) CD8 (+) thymocytes. Nat Immunol. 2002; 3 (5): 469-76.
56. Kim PJ, Pai SY, Brigl M, Besra GS, Gumperz J, Ho IC. GATA-3 regulates the development and function of invariant NKT cells. J Immunol. 2006; 177 (10): 6650-9.
57. Monteiro M, Almeida CF, Caridade M, Ribot JC, Duarte J, Agua-Doce A, Wollenberg I, Silva-Santos B, Graca L. Identification of regulatory Foxp3+ invariant NKT cells induced by TGF-beta. J Immunol. 2010; 185 (4): 2157-63.
58. Moreira-Teixeira L, Resende M, Coffre M, Devergne O, Herbeuval JP, Hermine O, Schneider E, Rogge L, Ruemmele FM, Dy M, Cordeiro-da-Silva A, Leite-de-Moraes MC. Proinflammatory environment dictates the IL-17-producing capacity of human invariant NKT cells. J Immunol. 2011; 186 (10): 5758-65.
59. Moreira-Teixeira L, Resende M, Devergne O, Herbeuval JP, Hermine O, Schneider E, Dy M, Cordeiro-da-Silva A, Leite-de-Moraes MC. Rapamycin combined with TGFbeta converts human invariant NKT cells into suppressive Foxp3+ regulatory cells. J Immunol. 2012; 188 (2): 624-31.
60. Yamane H, Paul WE. Early signaling events that underlie fate decisions of naive CD4 (+) T cells toward distinct T-helper cell subsets. Immunol Rev. 2013; 252 (1): 12-23.
61. Hirahara K, Poholek A, Vahedi G, Laurence A, Kanno Y, Milner JD, O'Shea JJ. Mechanisms underlying helper T-cell plasticity: implications for immune-mediated disease. J Allergy Clin Immunol. 2013; 131 (5): 1276-87.
62. Bromley SK, Mempel TR, Luster AD. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat Immunol. 2008; 9 (9): 970-80.
63. Doisne JM, Becourt C, Amniai L, Duarte N, Le Luduec JB, Eberl G, Benlagha K. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma) t+ and respond preferentially under inflammatory conditions. J Immunol. 2009; 183 (3): 2142-9.
64. Thomas SY, Hou R, Boyson JE, Means TK, Hess C, Olson DP, Strominger JL, Brenner MB, Gumperz JE, Wilson SB, Luster AD. CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. J Immunol. 2003; 171 (5): 2571-80.
65. Kim CH, Johnston B, Butcher EC. Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24 (+) V beta 11 (+) NKT cell subsets with distinct cytokine-producing capacity. Blood. 2002; 100 (1): 11-6.
66. Wallace KL, Marshall MA, Ramos SI, Lannigan JA, Field JJ, Strieter RM, Linden J. NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-gamma and CXCR3 chemokines. Blood. 2009; 114 (3): 667-76.
67. Lee PT, Benlagha K, Teyton L, Bendelac A. Distinct functional lineages of human V (alpha) 24 natural killer T cells. J Exp Med. 2002; 195 (5): 637-41.
68. Skold M, Faizunnessa NN, Wang CR, Cardell S. CD1dspecific NK1. 1+ T cells with a transgenic variant TCR. J Immunol. 2000; 165 (1): 168-74.
69. Arrenberg P, Halder R, Dai Y, Maricic I, Kumar V. Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a betalinked self-glycolipid. Proc Natl Acad Sci U S A. 2010; 107 (24): 10984-9.
70. Rolf J, Berntman E, Stenstrom M, Smith EM, Mansson R, Stenstad H, Yamagata T, Agace W, Sigvardsson M, Cardell SL. Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets. Mol Immunol. 2008; 45 (9): 2607-20.
71. Tatituri RV, Watts GF, Bhowruth V, Barton N, Rothchild A, Hsu FF, Almeida CF, Cox LR, Eggeling L, Cardell S, Rossjohn J, Godfrey DI, Behar SM, Besra GS, Brenner MB Brigl M. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci U S A. 2013; 110 (5): 1827-32.
72. Chang PP, Barral P, Fitch J, Pratama A, Ma CS, Kallies A, Hogan JJ, Cerundolo V, Tangye SG, Bittman R, Nutt SL, Brink R, Godfrey DI, Batista FD, Vinuesa CG. Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses. Nat Immunol. 2011; 13 (1): 35-43.
73. King IL, Fortier A, Tighe M, Dibble J, Watts GF, Veerapen N, Haberman AM, Besra GS, Mohrs M, Brenner MB, Leadbetter EA. Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. Nat Immunol. 2011; 13 (1): 44-50.
74. Gleimer M, von Boehmer H, Kreslavsky T. PLZF Controls the Expression of a Limited Number of Genes Essential for NKT Cell Function. Frontiers Immunol. 2012; 3: 374.
75. Johnston B, Kim CH, Soler D, Emoto M, Butcher EC. Differential chemokine responses and homing patterns of murine TCR alpha beta NKT cell subsets. J Immunol. 2003; 171 (6): 2960-9.
76. Bai L, Constantinides MG, Thomas SY, Reboulet R, Meng F, Koentgen F, Teyton L, Savage PB, Bendelac A. Distinct APCs explain the cytokine bias of alphagalactosylceramide variants in vivo. J Immunol. 2012; 188 (7): 3053-61.
77. Nakayamada S, Takahashi H, Kanno Y, O'Shea JJ. Helper T cell diversity and plasticity. Curr Opin Immunol. 2012; 24 (3): 297-302.
78. Juno JA, Keynan Y, Fowke KR. Invariant NKT cells: regulation and function during viral infection. PLoS Pathogens. 2012; 8 (8): e1002838.
79. Ohkura N, Kitagawa Y, Sakaguchi S. Development and maintenance of regulatory T cells. Immunity. 2013; 38 (3): 414-23.
80. Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature. 2010; 463 (7282): 808-12.
81. Cobbold SP, Castejon R, Adams E, Zelenika D, Graca L, Humm S, Waldmann H. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J Immunol. 2004; 172 (10): 6003-10.
82. Mucida D, Kutchukhidze N, Erazo A, Russo M, Lafaille JJ, Curotto de Lafaille MA. Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest. 2005; 115 (7): 1923-33.
83. Duarte J, Agua-Doce A, Oliveira VG, Fonseca JE, Graca L. Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice. PLoS One. 2010; 5 (5): e10558.
84. Duarte J, Carrie N, Oliveira VG, Almeida C, Agua-Doce A, Rodrigues L, Simas JP, Mars LT, Graca L. T cell apoptosis and induction of Foxp3+ regulatory T cells underlie therapeutic efficacy of CD4 blockade in experimental autoimmune encephalomyelitis. J Immunol. 2012; 189 (4): 1680-8.
85. Oliveira VG, Caridade M, Paiva RS, Demengeot J, Graca L. Sub-optimal CD4+ T-cell activation triggers autonomous TGF-beta-dependent conversion to Foxp3+ regulatory T cells. Eur J Immunol. 2011; 41 (5): 1249-55.
86. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, Srivastava M, Divekar DP, Beaton L, Hogan JJ, Fagarasan S, Liston A, Smith KG, Vinuesa CG. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med. 2011; 17 (8): 975-82.
87. Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S, Wang YH, Lim H, Reynolds JM, Zhou XH, Fan HM, Liu ZM, Neelapu SS, Dong C. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med. 2011; 17 (8): 983-8.
88. Wollenberg I, Agua-Doce A, Hernandez A, Almeida C, Oliveira VG, Faro J, Graca L. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol. 2011; 187 (9): 4553-60.