Induction of CD4＋ Regulatory and Polarized Effector/helper T Cells by Dendritic Cells

다국어 초록 (Multilingual Abstract)

Dendritic cells (DCs) are considered to play major roles during the induction of T cell immune responses as well as the maintenance of T cell tolerance. Naive CD4 ＋ T cells have been shown to respond with high plasticity to signals inducing their polarization into effector/helper or regulatory T cells. Data obtained from in vitro generated bonemarrow (BM)-derived DCs as well as genetic mouse models revealed an important but not exclusive role of DCs in shaping CD4 ＋ T cell responses. Besides the specialization of some conventional DC subsets for the induction of polarized immunity, also the maturation stage, activation of specialized transcription factors and the cytokine production of DCs have major impact on CD4 ＋ T cells. Since in vitro generated BM-DCs show a high diversity to shape CD4 ＋ T cells and their high similarity to monocyte-derived DCs in vivo, this review reports data mainly on BM-DCs in this process and only touches the roles of transcription factors or of DC subsets, which have been discussed elsewhere. Here, recent findings on 1) the conversion of naive into anergic and further into Foxp3 − regulatory T cells (Treg) by immature DCs, 2) the role of RelB in steady state migratory DCs (ssmDCs) for conversion of naive T cells into Foxp3 ＋ Treg, 3) the DC maturation signature for polarized Th2 cell induction and 4) the DC source of IL-12 for Th1 induction are discussed.

참고문헌 (Reference)

1 Reinhardt, R. L., "Visualization of IL-12/23p40 in vivo reveals immunostimulatory dendritic cell migrants that promote Th1differentiation" 177 : 1618-1627, 2006

2 Casaravilla, C., "Unconventional maturation of dendritic cells induced by particles from the laminated layer of larval Echinococcus granulosus" 82 : 3164-3176, 2014

3 Wyzgol, A., "Trimer stabilization, oligomerization, and antibody-mediated cell surface immobilization improve the activity of soluble trimers of CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligand" 183 : 1851-1861, 2009

4 Zheng, Y., "Transcriptional regulator early growth response gene 2(Egr2) is required for T cell anergy in vitro and in vivo" 209 : 2157-2163, 2012

5 Macian, F., "Transcriptional mechanisms underlying lymphocyte tolerance" 109 : 719-731, 2002

6 Oestreich, K. J., "Transcriptional mechanisms that regulate T helper 1 cell differentiation" 24 : 191-195, 2012

7 Raker, V. K., "Tolerogenic dendritic cells for regulatory T cell induction in man" 6 : 569-, 2015

8 Theiner, G., "The mast cell mediator PGD2 suppresses IL-12 release by dendritic cells leading to Th2 polarized immune responses in vivo" 211 : 463-472, 2006

9 Verdoodt, B., "The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T cell anergy" 33 : 3154-3163, 2003

10 Sixt, M., "The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node" 22 : 19-29, 2005

11 Tang, H., "The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling" 11 : 608-617, 2010

12 Littman, D. R., "Th17 and regulatory T cells in mediating and restraining inflammation" 140 : 845-858, 2010

13 Theiner, G., "TLR9 cooperates with TLR4 to increase IL-12 release by murine dendritic cells" 45 : 244-252, 2008

14 van, P. N., "T-cell-receptor-dependent signal intensity dominantly controls CD4(＋) T cell polarization in vivo" 41 : 63-74, 2014

15 Burkly, L. C., "T-cell tolerance by clonal anergy in transgenic mice with nonlymphoid expression of MHC class II I-E" 342 : 564-566, 1989

16 Abdi, K., "T-cell control of IL-12p75 production" 64 : 83-92, 2006

17 Macian, F., "T-cell anergy" 16 : 209-216, 2004

18 O'Garra, A., "T(H)1 cells control themselves by producing interleukin-10" 7 : 425-428, 2007

19 Langenkamp, A., "T cell priming by dendritic cells: thresholds for proliferation, differentiation and death and intraclonal functional diversification" 32 : 2046-2054, 2002

20 Schwartz, R. H., "T cell anergy" 21 : 305-334, 2003

21 Azukizawa, H., "Steady state migratory RelB ＋langerin ＋dermal dendritic cells mediate peripheral induction of antigen-specific CD4＋CD25＋Foxp3＋regulatory T cells" 41 : 1420-1434, 2011

22 Idoyaga, J., "Specialized role of migratory dendritic cells in peripheral tolerance induction" 123 : 844-854, 2013

23 Waithman, J., "Skin-derived dendritic cells can mediate deletional tolerance of class I-restricted self-reactive T cells" 179 : 4535-4541, 2007

24 Pletinckx, K., "Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2-cell responses" 41 : 3479-3494, 2011

25 Mescher, M. F., "Signals required for programming effector and memory development by CD8＋T cells" 211 : 81-92, 2006

26 Ahlers, J. D., "Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression: IL-12 and tumor necrosis factor-alpha synergize for IL-12R expression at low antigen dose" 13 : 1433-1442, 2001

27 Huynh, A., "Signals and pathways controlling regulatory T cells" 258 : 117-131, 2014

28 Wells, A. D., "Signaling through CD28 and CTLA-4 controls two distinct forms of T cell anergy" 108 : 895-903, 2001

29 Curtsinger, J. M., "Signal 3 availability limits the CD8 T cell response to a solid tumor" 178 : 6752-6760, 2007

30 de, J. R., "Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients" 280 : 1435-1438, 1998

31 Schulz, E. G., "Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12" 30 : 673-683, 2009

32 Rogge, L., "Selective expression of an interleukin-12 receptor component by human T helper 1 cells" 185 : 825-831, 1997

33 Kawabe, Y., "Selective anergy of V beta 8＋, CD4＋ T cells in Staphylococcus enterotoxin B-primed mice" 172 : 1065-1070, 1990

34 Napolitani, G., "Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells" 6 : 769-776, 2005

35 Pletinckx, K., "Role of dendritic cell maturity/costimulation for generation, homeostasis, and suppressive activity of regulatory T cells" 2 : 39-, 2011

36 Lutz, M. B., "Revisiting the tolerogenicity of epidermal Langerhans cells" 88 : 381-386, 2010

37 Menges, M., "Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity" 195 : 15-21, 2002

38 Jooss, K., "Regulatory function of in vivo anergized CD4(＋) T cells" 98 : 8738-8743, 2001

39 Szabo, S. J., "Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells" 185 : 817-824, 1997

40 Weih, F., "Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway" 195 : 91-105, 2003

41 Freeman, B. E., "Regulation of innate CD8＋T-cell activation mediated by cytokines" 109 : 9971-9976, 2012

42 Baine, I., "Regulation of T-cell tolerance by calcium/NFAT signaling" 231 : 225-240, 2009

43 Sakaguchi, S., "Re-establishing immunological self-tolerance in autoimmune disease" 18 : 54-58, 2012

44 O'Garra, A., "Quantitative events determine the differentiation and function of helper T cells" 12 : 288-294, 2011

45 Akbari, O., "Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen" 2 : 725-731, 2001

46 Joo, H., "Opposing roles of Dectin-1 expressed on human plasmacytoid dendritic cells and myeloid dendritic cells in Th2polarization" 195 : 1723-1731, 2015

47 Ziegler-Heitbrock, L., "Nomenclature of monocytes and dendritic cells in blood" 116 : e74-e80, 2010

48 Pulendran, B., "New paradigms in type 2immunity" 337 : 431-435, 2012

49 Gabrysova, L., "Negative feedback control of the autoimmune response through antigen-induced differentiation of IL-10-secreting Th1 cells" 206 : 1755-1767, 2009

50 Bajenoff, M., "Natural killer cell behavior in lymph nodes revealed by static and real-time imaging" 203 : 619-631, 2006

51 Andris, F., "Naive T cells are resistant to anergy induction by anti-CD3antibodies" 173 : 3201-3208, 2004

52 Goldszmid, R. S., "NK cell-derived interferon-gamma orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection" 36 : 1047-1059, 2012

53 Hayden, M. S., "NF-kappaB, the first quarter-century: remarkable progress and outstanding questions" 26 : 203-234, 2012

54 Chow, K. V., "Monocyte-derived dendritic cells promote Th polarization, whereas conventional dendritic cells promote Th proliferation" 196 : 624-636, 2016

55 Fathman, C. G., "Molecular mechanisms of CD4＋ T-cell anergy" 7 : 599-609, 2007

56 Cheong, C., "Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(＋) dendritic cells for immune T cell areas" 143 : 416-429, 2010

57 Schijns, V. E., "Mice lacking IL-12 develop polarized Th1 cells during viral infection" 160 : 3958-3964, 1998

58 Travis, M. A., "Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice" 449 : 361-365, 2007

59 Cella, M., "Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12and enhances T cell stimulatory capacity: T-T help via APC activation" 184 : 747-752, 1996

60 Langenkamp, A., "Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells" 1 : 311-316, 2000

61 Dorrie, J., "Introduction of functional chimeric E/L-selectin by RNA electroporation to target dendritic cells from blood to lymph nodes" 57 : 467-477, 2008

62 Heufler, C., "Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells" 26 : 659-668, 1996

63 Mattner, F., "Interleukin-12 is indispensable for protective immunity against Leishmania major" 65 : 4378-4383, 1997

64 Trinchieri, G., "Interleukin-12 and the regulation of innate resistance and adaptive immunity" 3 : 133-146, 2003

65 Buer, J., "Interleukin 10 secretion and impaired effector function of major histocompatibility complex class II-restricted T cells anergized in vivo" 187 : 177-183, 1998

66 Hochrein, H., "Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12production by mouse and human dendritic cells" 192 : 823-833, 2000

67 Jenkins, M. K., "Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody" 144 : 16-22, 1990

68 Sporri, R., "Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4＋T cell populations lacking helper function" 6 : 163-170, 2005

69 Perez, V. L., "Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement" 6 : 411-417, 1997

70 Sloan-Lancaster, J., "Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells" 363 : 156-159, 1993

71 Valdor, R., "Induction and stability of the anergic phenotype in T cells" 25 : 313-320, 2013

72 Martin-Fontecha, A., "Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1priming" 5 : 1260-1265, 2004

73 Reis e Sousa, "In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas" 186 : 1819-1829, 1997

74 Apostolou, I., "In vivo instruction of suppressor commitment in naive T cells" 199 : 1401-1408, 2004

75 Rellahan, B. L., "In vivo induction of anergy in peripheral V beta 8＋ T cells by staphylococcal enterotoxin B" 172 : 1091-1100, 1990

76 Ingulli, E., "In vivo detection of dendritic cell antigen presentation to CD4(＋)T cells" 185 : 2133-2141, 1997

77 Sam, H., "In vivo IL-12 production and IL-12 receptors beta1 and beta2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria" 162 : 1582-1589, 1999

78 Schumann, K., "Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells" 32 : 703-713, 2010

79 Lutz, M. B., "Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?" 23 : 445-449, 2002

80 Pletinckx, K., "Immature dendritic cells convert anergic nonregulatory T cells into Foxp3−IL-10＋regulatory T cells by engaging CD28 and CTLA-4" 45 : 480-491, 2015

81 Berger, T. G., "Immature and maturation-resistant human dendritic cells generated from bone marrow require two stimulations to induce T cell anergy in vitro" 4 : e6645-, 2009

82 Muller, U., "IL-12-independent IFN-gamma production by T cells in experimental Chagas' disease is mediated by IL-18" 167 : 3346-3353, 2001

83 Kalinski, P., "IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells" 159 : 28-35, 1997

84 Grohmann, U., "IL-12 acts directly on DC to promote nuclear localization of NF-kappaB and primes DC for IL-12 production" 9 : 315-323, 1998

85 O'Garra, A., "IL-10-producing and naturally occurring CD4＋Tregs: limiting collateral damage" 114 : 1372-1378, 2004

86 Redpath, S. A., "ICOS controls Foxp3(＋) regulatory T-cell expansion, maintenance and IL-10production during helminth infection" 43 : 705-715, 2013

87 Amodio, G., "Human tolerogenic DC-10:perspectives for clinical applications" 1 : 14-, 2012

88 Lutz, M. B., "How quantitative differences in dendritic cell maturation can direct T1/T2-cell polarization" 2 : e22796-, 2013

89 Baratin, M., "Homeostatic NF-kappaB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance" 42 : 627-639, 2015

90 Wegner, J., "High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens" 126 : 185-194, 2015

91 Knippertz, I., "Generation of human dendritic cells that simultaneously secrete IL-12 and have migratory capacity by adenoviral gene transfer of hCD40L in combination with IFN-gamma" 32 : 524-538, 2009

92 Luft, T., "Functionally distinct dendritic cell (DC)populations induced by physiologic stimuli: prostaglandin E(2)regulates the migratory capacity of specific DC subsets" 100 : 1362-1372, 2002

93 Knoechel, B., "Functional and molecular comparison of anergic and regulatory T lymphocytes" 176 : 6473-6483, 2006

94 Lechner, O., "Fingerprints of anergic T cells" 11 : 587-595, 2001

95 Qi, H., "Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells" 312 : 1672-1676, 2006

96 Futagawa, T., "Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells" 14 : 275-286, 2002

97 Nono, J. K., "Excretory/secretory-products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro" 6 : e1516-, 2012

98 Jeon, M. S., "Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction" 21 : 167-177, 2004

99 Chakraborty, N. G., "Emergence of regulatory CD4＋T cell response to repetitive stimulation with antigen-presenting cells in vitro: implications in designing antigen-presenting cell-based tumor vaccines" 162 : 5576-5583, 1999

100 Miah, M. A., "Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity" 43 : 2484-2496, 2013

101 Safford, M., "Egr-2 and Egr-3 are negative regulators of T cell activation" 6 : 472-480, 2005

102 Puccetti, P., "Effects of IL-12 and IL-23 on antigen-presenting cells at the interface between innate and adaptive immunity" 22 : 373-390, 2002

103 Moretta, L., "Effector and regulatory events during natural killer-dendritic cell interactions" 214 : 219-228, 2006

104 De, S. T., "Effect of interleukin-10 on dendritic cell maturation and function" 27 : 1229-1235, 1997

105 Harris, J. E., "Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4＋T cells" 173 : 7331-7338, 2004

106 Kriegel, M. A., "E3 ubiquitin ligase GRAIL controls primary T cell activation and oral tolerance" 106 : 16770-16775, 2009

107 Perona-Wright, G., "Distinct sources and targets of IL-10 during dendritic cell-driven Th1 and Th2 responses in vivo" 36 : 2367-2375, 2006

108 Sallusto, F., "Distinct patterns and kinetics of chemokine production regulate dendritic cell function" 29 : 1617-1625, 1999

109 Tjota, M. Y., "Distinct dendritic cell subsets actively induce Th2 polarization" 31 : 44-50, 2014

110 Itano, A. A., "Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity" 19 : 47-57, 2003

111 Pape, K. A., "Direct evidence that functionally impaired CD4＋T cells persist in vivo following induction of peripheral tolerance" 160 : 4719-4729, 1998

112 Elloso, M. M., "Differential requirement of CD28 for IL-12 receptor expression and function in CD4(＋) and CD8(＋) T cells" 31 : 384-395, 2001

113 Lutz, M. B., "Differential functions of IL-4 receptor types I and II for dendritic cell maturation and IL-12 production and their dependency on GM-CSF" 169 : 3574-3580, 2002

114 Steinman, R. M., "Dendritic cells: translating innate to adaptive immunity" 311 : 17-58, 2006

115 Longhi, M. P., "Dendritic cells require a systemic type I interferon response to mature and induce CD4＋Th1 immunity with poly IC as adjuvant" 206 : 1589-1602, 2009

116 Voigtlander, C., "Dendritic cells matured with TNF can be further activated in vitro and after subcutaneous injection in vivo which converts their tolerogenicity into immunogenicity" 29 : 407-415, 2006

117 Wykes, M., "Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response" 161 : 1313-1319, 1998

118 Walsh, K. P., "Dendritic cells and other innate determinants of T helper cell polarisation" 34 : 521-530, 2013

119 Ramirez-Pineda, J. R., "Dendritic cells (DC) activated by CpG DNA ex vivo are potent inducers of host resistance to an intracellular pathogen that is independent of IL-12 derived from the immunizing DC" 172 : 6281-6289, 2004

120 Berberich, C., "Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens" 170 : 3171-3179, 2003

121 Naik, S. H., "Demystifying the development of dendritic cell subtypes, a little" 86 : 439-452, 2008

122 Maldonado-Lopez, R., "Cytokines regulate the capacity of CD8alpha(＋) and CD8alpha(−) dendritic cells to prime Th1/Th2 cells in vivo" 167 : 4345-4350, 2001

123 Wilcox, R. A., "Cutting edge: Expression of functional CD137receptor by dendritic cells" 168 : 4262-4267, 2002

124 Rammensee, H. G., "Clonal anergy induced in mature V beta 6＋ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells" 339 : 541-544, 1989

125 Pulecio, J., "Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse" 207 : 2719-2732, 2010

126 Walunas, T. L., "CTLA-4ligation blocks CD28-dependent T cell activation" 183 : 2541-2550, 1996

127 Brunner, M. C., "CTLA-4-Mediated inhibition of early events of T cell proliferation" 162 : 5813-5820, 1999

128 Greenwald, R. J., "CTLA-4 regulates induction of anergy in vivo" 14 : 145-155, 2001

129 Krummel, M. F., "CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells" 183 : 2533-2540, 1996

130 Rudd, C. E., "CD28 and CTLA-4 coreceptor expression and signal transduction" 229 : 12-26, 2009

131 Ohl, L., "CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions" 21 : 279-288, 2004

132 Weber, C., "CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice" 121 : 2898-2910, 2011

133 Steinman, R. M., "Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance" 99 : 351-358, 2002

134 Gabrysova, L., "Antigenic strength controls the generation of antigen-specific IL-10-secreting T regulatory cells" 40 : 1386-1395, 2010

135 Lutz, M. B., "An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow" 223 : 77-92, 1999

136 Soares, H., "A subset of dendritic cells induces CD4+T cells to produce IFN-gamma by an IL-12-independent but CD70-dependent mechanism in vivo" 204 : 1095-1106, 2007

137 Fontenot, J. D., "A function for interleukin 2 in Foxp3-expressing regulatory T cells" 6 : 1142-1151, 2005

138 Groux, H., "A CD4＋T-cell subset inhibits antigen-specific T-cell responses and prevents colitis" 389 : 737-742, 1997

139 Laderach, D., "4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12" 226 : 37-44, 2003