[1] Abbas, A.K., Murphy, K.M., and Sher, A. (1996). Functional diversity of helper T lymphocytes. Nature 383, 787-793 .8893001
[2] Agarwal, S., Avni, O., and Rao, A. (2000). Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 12, 643-652 .10894164
[3] Agarwal, S., and Rao, A. (1998). Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9, 765-775 .9881967
[4] Allen, C.D., Okada, T., and Cyster, J.G. (2007). Germinal-center organization and cellular dynamics. Immunity 27, 190-202 .17723214
[5] Amsen, D., Antov, A., Jankovic, D., Sher, A., Radtke, F., Souabni, A., Busslinger, M., McCright, B., Gridley, T., and Flavell, R.A. (2007). Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 27, 89-99 .17658279
[6] Amsen, D., Blander, J.M., Lee, G.R., Tanigaki, K., Honjo, T., and Flavell, R.A. (2004). Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 117, 515-526 .15137944
[7] Angkasekwinai, P., Chang, S.H., Thapa, M., Watarai, H., and Dong, C. (2010). Regulation of IL-9 expression by IL-25 signaling. Nat Immunol 11, 250-256 .20154671
[8] Ansel, K.M., McHeyzer-Williams, L.J., Ngo, V.N., McHeyzer-Williams, M.G., and Cyster, J.G. (1999). In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. J Exp Med 190, 1123-1134 .10523610
[9] Barolo, S., Walker, R.G., Polyanovsky, A.D., Freschi, G., Keil, T., and Posakony, J.W. (2000). A notch-independent activity of suppressor of hairless is required for normal mechanoreceptor physiology. Cell 103, 957-969 .11136980
[10] Beriou, G., Bradshaw, E.M., Lozano, E., Costantino, C.M., Hastings, W.D., Orban, T., Elyaman, W., Khoury, S.J., Kuchroo, V.K., Baecher-Allan, C., (2010). TGF-beta induces IL-9 production from human Th17 cells. J Immunol 185, 46-54 .20498357
[11] Bird, J.J., Brown, D.R., Mullen, A.C., Moskowitz, N.H., Mahowald, M.A., Sider, J.R., Gajewski, T.F., Wang, C.R., and Reiner, S.L. (1998). Helper T cell differentiation is controlled by the cell cycle. Immunity 9, 229-237 .9729043
[12] Breitfeld, D., Ohl, L., Kremmer, E., Ellwart, J., Sallusto, F., Lipp, M., and F?rster, R. (2000). Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192, 1545-1552 .11104797
[13] Brinkmann, V., Davis, M.D., Heise, C.E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E., Baumruker, T., Hiestand, P., (2002). The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 277, 21453-21457 .11967257
[14] Brusselle, G.G., Kips, J.C., Tavernier, J.H., van der Heyden, J.G., Cuvelier, C.A., Pauwels, R.A., and Bluethmann, H. (1994). Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy 24, 73-80 .8156448
[15] Brüstle, A., Heink, S., Huber, M., Rosenpl?nter, C., Stadelmann, C., Yu, P., Arpaia, E., Mak, T.W., Kamradt, T., and Lohoff, M. (2007). The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 8, 958-966 .17676043
[16] Busse, W.W., and Lemanske, R.F. Jr. (2001). Asthma. N Engl J Med 344, 350-362 .11172168
[17] Chang, H.C., Sehra, S., Goswami, R., Yao, W., Yu, Q., Stritesky, G.L., Jabeen, R., McKinley, C., Ahyi, A.N., Han, L., (2010). The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol 11, 527-534 .20431622
[18] Cohn, L., Tepper, J.S., and Bottomly, K. (1998). IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells. J Immunol 161, 3813-3816 .9780144
[19] Corry, D.B., Folkesson, H.G., Warnock, M.L., Erle, D.J., Matthay, M.A., Wiener-Kronish, J.P., and Locksley, R.M. (1996). Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 183, 109-117 .8551213
[20] Yusuf, I., Kageyama, R., Monticelli, L., Johnston, R.J., Ditoro, D., Hansen, K., Barnett, B., and Crotty, S. (2010). Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150). J Immunol 185, 190-202 .20525889
[21] Dardalhon, V., Awasthi, A., Kwon, H., Galileos, G., Gao, W., Sobel, R.A., Mitsdoerffer, M., Strom, T.B., Elyaman, W., Ho, I.C., (2008). IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol 9, 1347-1355 .18997793
[22] Dufort, F.J., Bleiman, B.F., Gumina, M.R., Blair, D., Wagner, D.J., Roberts, M.F., Abu-Amer, Y., and Chiles, T.C. (2007). Cutting edge: IL-4-mediated protection of primary B lymphocytes from apoptosis via Stat6-dependent regulation of glycolytic metabolism. J Immunol 179, 4953-4957 .17911579
[23] Fang, T.C., Yashiro-Ohtani, Y., Del Bianco, C., Knoblock, D.M., Blacklow, S.C., and Pear, W.S. (2007). Notch directly regulates Gata3 expression during T helper 2 cell differentiation. Immunity 27, 100-110 .17658278
[24] Fazilleau, N., McHeyzer-Williams, L.J., Rosen, H., and McHeyzer-Williams, M.G. (2009). The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol 10, 375-384 .19252493
[25] F?rster, R., Mattis, A.E., Kremmer, E., Wolf, E., Brem, G., and Lipp, M. (1996). A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 87, 1037-1047 .8978608
[26] Gessner, A., Blum, H., and R?llinghoff, M. (1993). Differential regulation of IL-9-expression after infection with Leishmania major in susceptible and resistant mice. Immunobiology 189, 419-435 .8125519
[27] Harris, N.L., Watt, V., Ronchese, F., and Le Gros, G. (2002). Differential T cell function and fate in lymph node and nonlymphoid tissues. J Exp Med 195, 317-326 .11828006
[28] Hegazy, A.N., Peine, M., Helmstetter, C., Panse, I., Fr?hlich, A., Bergthaler, A., Flatz, L., Pinschewer, D.D., Radbruch, A., and L?hning, M. (2010). Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity 32, 116-128 .20079668
[29] Herrick, C.A., and Bottomly, K. (2003). To respond or not to respond: T cells in allergic asthma. Nat Rev Immunol 3, 405-412 .12766762
[30] Ho, I.C., and Glimcher, L.H. (2002). Transcription: tantalizing times for T cells. Cell 109, S109-S120 .11983157
[31] Ho, I.C., Hodge, M.R., Rooney, J.W., and Glimcher, L.H. (1996). The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85, 973-983 .8674125
[32] Hutchins, A.S., Mullen, A.C., Lee, H.W., Sykes, K.J., High, F.A., Hendrich, B.D., Bird, A.P., and Reiner, S.L. (2002). Gene silencing quantitatively controls the function of a developmental trans-activator. Mol Cell 10, 81-91 .12150909
[33] Johnston, R.J., Poholek, A.C., DiToro, D., Yusuf, I., Eto, D., Barnett, B., Dent, A.L., Craft, J., and Crotty, S. (2009). Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325, 1006-1010 .19608860
[34] Kaplan, M.H., Schindler, U., Smiley, S.T., and Grusby, M.J. (1996). Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4, 313-319 .8624821
[35] Kim, J., Woods, A., Becker-Dunn, E., and Bottomly, K. (1985). Distinct functional phenotypes of cloned Ia-restricted helper T cells. J Exp Med 162, 188-201 .3159823
[36] King, I.L., and Mohrs, M. (2009). IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J Exp Med 206, 1001-1007 .19380638
[37] Kips, J.C., Brusselle, G.G., Joos, G.F., Peleman, R.A., Devos, R.R., Tavernier, J.H., and Pauwels, R.A. (1995). Importance of interleukin-4 and interleukin-12 in allergen-induced airway changes in mice. Int Arch Allergy Immunol 107, 115-118 .7613115
[38] Kopf, M., Le Gros, G., Coyle, A.J., Kosco-Vilbois, M., and Brombacher, F. (1995). Immune responses of IL-4, IL-5, IL-6 deficient mice. Immunol Rev 148, 45-69 .8825282
[39] Lee, G.R., Fields, P.E., and Flavell, R.A. (2001). Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 14, 447-459 .11336690
[40] Lee, Y.K., Turner, H., Maynard, C.L., Oliver, J.R., Chen, D., Elson, C.O., and Weaver, C.T. (2009). Late developmental plasticity in the T helper 17 lineage. Immunity 30, 92-107 .19119024
[41] Li, Z., Zhang, Y., Liu, Z., Wu, X., Zheng, Y., Tao, Z., Mao, K., Wang, J., Lin, G., Tian, L., (2011). ECM1 controls T(H)2 cell egress from lymph nodes through re-expression of S1P(1). Nat Immunol 12, 178-185 .21217760
[42] Linterman, M.A., Beaton, L., Yu, D., Ramiscal, R.R., Srivastava, M., Hogan, J.J., Verma, N.K., Smyth, M.J., Rigby, R.J., and Vinuesa, C.G. (2010). IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med 207, 353-363 .20142429
[43] Liu, Y.J., Joshua, D.E., Williams, G.T., Smith, C.A., Gordon, J., and MacLennan, I.C. (1989). Mechanism of antigen-driven selection in germinal centres. Nature 342, 929-931 .2594086
[44] Liu, Z., Li, Z., Mao, K., Zou, J., Wang, Y., Tao, Z., Lin, G., Tian, L., Ji, Y., Wu, X., (2009). Dec2 promotes Th2 cell differentiation by enhancing IL-2R signaling. J Immunol 183, 6320-6329 .19880450
[45] Lommatzsch, M., Julius, P., Kuepper, M., Garn, H., Bratke, K., Irmscher, S., Luttmann, W., Renz, H., Braun, A., and Virchow, J.C. (2006). The course of allergen-induced leukocyte infiltration in human and experimental asthma. J Allergy Clin Immunol 118, 91-97 .16815143
[46] MacLennan, I.C. (1994). Germinal centers. Annu Rev Immunol 12, 117-139 .8011279
[47] Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.J., Card, D., Keohane, C., (2002). Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296, 346-349 .11923495
[48] Martinez-Valdez, H., Guret, C., de Bouteiller, O., Fugier, I., Banchereau, J., and Liu, Y.J. (1996). Human germinal center B cells express the apoptosis-inducing genes Fas, c-myc, P53, and Bax but not the survival gene bcl-2. J Exp Med 183, 971-977 .8642300
[49] Medoff, B.D., Thomas, S.Y., and Luster, A.D. (2008). T cell trafficking in allergic asthma: the ins and outs. Annu Rev Immunol 26, 205-232 .18304002
[50] Mohrs, M., Blankespoor, C.M., Wang, Z.E., Loots, G.G., Afzal, V., Hadeiba, H., Shinkai, K., Rubin, E.M., and Locksley, R.M. (2001). Deletion of a coordinate regulator of type 2 cytokine expression in mice. Nat Immunol 2, 842-847 .11526400
[51] Moreau, J.F., Dechanet-Merville, J., and Taupin, J.L. (2000). T cells and cellular immunity; T receptors (structure, diversity, repertory); differentiation antigens (CD4, CD8); activation; auxillary T cells and immunoregulation; lymphokines (interferons, TNF, IL-1, IL-2, IL-4) and cytotoxicity; concept of cellular immunity deficit. Rev Prat 50, 2183-2193 .11213465
[52] Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A., and Coffman, R.L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136, 2348-2357 .2419430
[53] Mullen, A.C., High, F.A., Hutchins, A.S., Lee, H.W., Villarino, A.V., Livingston, D.M., Kung, A.L., Cereb, N., Yao, T.P., Yang, S.Y., (2001). Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907-1910 .11397944
[54] Murphy, K.M., and Reiner, S.L. (2002). The lineage decisions of helper T cells. Nat Rev Immunol 2, 933-944 .12461566
[55] Nelms, K., Keegan, A.D., Zamorano, J., Ryan, J.J., and Paul, W.E. (1999). The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17, 701-738 .10358772
[56] Nurieva, R.I., Chung, Y., Hwang, D., Yang, X.O., Kang, H.S., Ma, L., Wang, Y.H., Watowich, S.S., Jetten, A.M., Tian, Q., (2008). Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29, 138-149 .18599325
[57] Nurieva, R.I., Chung, Y., Martinez, G.J., Yang, X.O., Tanaka, S., Matskevitch, T.D., Wang, Y.H., and Dong, C. (2009). Bcl6 mediates the development of T follicular helper cells. Science 325, 1001-1005 .19628815
[58] O’Shea, J.J., Lahesmaa, R., Vahedi, G., Laurence, A., and Kanno, Y. (2011). Genomic views of STAT function in CD4+ T helper cell differentiation. Nat Rev Immunol 11, 239-250 .21436836
[59] Ong, C.T., Sedy, J.R., Murphy, K.M., and Kopan, R. (2008). Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition. PLoS One 3, e2823.18665263
[60] Ouyang, W., L?hning, M., Gao, Z., Assenmacher, M., Ranganath, S., Radbruch, A., and Murphy, K.M. (2000). Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12, 27-37 .10661403
[61] Paul, W.E., and Ohara, J. (1987). B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol 5, 429-459 .3297106
[62] Reinhardt, R.L., Liang, H.E., and Locksley, R.M. (2009). Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 10, 385-393 .19252490
[63] Rengarajan, J., Mowen, K.A., McBride, K.D., Smith, E.D., Singh, H., and Glimcher, L.H. (2002). Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression. J Exp Med 195, 1003-1012 .11956291
[64] Rivera, J., Proia, R.L., and Olivera, A. (2008). The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat Rev Immunol 8, 753-763 .18787560
[65] Robinson, D., Hamid, Q., Bentley, A., Ying, S., Kay, A.B., and Durham, S.R. (1993). Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol 92, 313-324 .8349942
[66] Robinson, D.S., Hamid, Q., Ying, S., Tsicopoulos, A., Barkans, J., Bentley, A.M., Corrigan, C., Durham, S.R., and Kay, A.B. (1992). Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326, 298-304 .1530827
[67] Rothoeft, T., Gonschorek, A., Bartz, H., Anhenn, O., and Schauer, U. (2003). Antigen dose, type of antigen-presenting cell and time of differentiation contribute to the T helper 1/T helper 2 polarization of naive T cells. Immunology 110, 430-439 .14632640
[68] Schaerli, P., Willimann, K., Lang, A.B., Lipp, M., Loetscher, P., and Moser, B. (2000). CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192, 1553-1562 .11104798
[69] Schmitt, E., Germann, T., Goedert, S., Hoehn, P., Huels, C., Koelsch, S., Kühn, R., Müller, W., Palm, N., and Rüde, E. (1994). IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma. J Immunol 153, 3989-3996 .7930607
[70] Schwab, S.R., and Cyster, J.G. (2007). Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol 8, 1295-1301 .18026082
[71] Schweitzer, A.N., Borriello, F., Wong, R.C., Abbas, A.K., and Sharpe, A.H. (1997). Role of costimulators in T cell differentiation: studies using antigen-presenting cells lacking expression of CD80 or CD86. J Immunol 158, 2713-2722 .9058805
[72] Staudt, V., Bothur, E., Klein, M., Lingnau, K., Reuter, S., Grebe, N., Gerlitzki, B., Hoffmann, M., Ulges, A., Taube, C., (2010). Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells. Immunity 33, 192-202 .20674401
[73] Szabo, S.J., Kim, S.T., Costa, G.L., Zhang, X., Fathman, C.G., and Glimcher, L.H. (2000). A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655-669 .10761931
[74] Szabo, S.J., Sullivan, B.M., Stemmann, C., Satoskar, A.R., Sleckman, B.P., and Glimcher, L.H. (2002). Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295, 338-342 .11786644
[75] Takahashi, Y., Ohta, H., and Takemori, T. (2001). Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire. Immunity 14, 181-192 .11239450
[76] Tanaka, S., Motomura, Y., Suzuki, Y., Yagi, R., Inoue, H., Miyatake, S., and Kubo, M. (2011). The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in T(H)2 cells. Nat Immunol 12, 77-85 .21131966
[77] Thomas, S.Y., Banerji, A., Medoff, B.D., Lilly, C.M., and Luster, A.D. (2007). Multiple chemokine receptors, including CCR6 and CXCR3, regulate antigen-induced T cell homing to the human asthmatic airway. J Immunol 179, 1901-1912 .17641057
[78] Veldhoen, M., Uyttenhove, C., van Snick, J., Helmby, H., Westendorf, A., Buer, J., Martin, B., Wilhelm, C., and Stockinger, B. (2008). Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9, 1341-1346 .18931678
[79] Walker, C., Bode, E., Boer, L., Hansel, T.T., Blaser, K., and Virchow, J.C. Jr. (1992). Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146, 109-115 .1626792
[80] Weaver, C.T., and Hatton, R.D. (2009). Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat Rev Immunol 9, 883-889 .19935807
[81] Wei, G., Wei, L., Zhu, J., Zang, C., Hu-Li, J., Yao, Z., Cui, K., Kanno, Y., Roh, T.Y., Watford, W.T., (2009). Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30, 155-167 .19144320
[82] Wurster, A.L., Rodgers, V.L., White, M.F., Rothstein, T.L., and Grusby, M.J. (2002). Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL. J Biol Chem 277, 27169-27175 .12023955
[83] Yang, X.O., Angkasekwinai, P., Zhu, J., Peng, J., Liu, Z., Nurieva, R., Liu, X., Chung, Y., Chang, S.H., Sun, B., (2009). Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment. Nat Immunol 10, 1260-1266 .19881507
[84] Yang, X.O., Nurieva, R., Martinez, G.J., Kang, H.S., Chung, Y., Pappu, B.P., Shah, B., Chang, S.H., Schluns, K.S., Watowich, S.S., (2008). Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29, 44-56 .18585065
[85] Yu, D., Rao, S., Tsai, L.M., Lee, S.K., He, Y., Sutcliffe, E.L., Srivastava, M., Linterman, M., Zheng, L., Simpson, N., (2009). The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457-468 .19631565
[86] Zaretsky, A.G., Taylor, J.J., King, I.L., Marshall, F.A., Mohrs, M., and Pearce, E.J. (2009). T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J Exp Med 206, 991-999 .19380637
[87] Zhu, J., Yamane, H., and Paul, W.E. (2010). Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28, 445-489 .20192806
[88] Zotos, D., Coquet, J.M., Zhang, Y., Light, A., D’Costa, K., Kallies, A., Corcoran, L.M., Godfrey, D.I., Toellner, K.M., Smyth, M.J., (2010). IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med 207, 365-378 .20142430
