Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Life of T Follicular Helper Cells

  • Suh, Woong-Kyung (Clinical Research Institute of Montreal (IRCM), University of Montreal, and McGill University)
  • Received : 2014.12.01
  • Accepted : 2014.12.04
  • Published : 2015.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Antibodies are powerful defense tools against pathogens but may cause autoimmune diseases when erroneously directed toward self-antigens. Thus, antibody producing cells are carefully selected, refined, and expanded in a highly regulated microenvironment (germinal center) in the peripheral lymphoid organs. A subset of T cells termed T follicular helper cells (Tfh) play a central role in instructing B cells to form a repertoire of antibody producing cells that provide life-long supply of high affinity, pathogenspecific antibodies. Therefore, understanding how Tfh cells arise and how they facilitate B cell selection and differentiation during germinal center reaction is critical to improve vaccines and better treat autoimmune diseases. In this review, I will summarise recent findings on molecular and cellular mechanisms underlying Tfh generation and function with an emphasis on T cell costimulation.

Keywords

References

  1. Allen, C.D., Okada, T., Tang, H.L., and Cyster, J.G. (2007). Imaging of germinal center selection events during affinity maturation. Science 315, 528-531. https://doi.org/10.1126/science.1136736
  2. Arnold, C.N., Campbell, D.J., Lipp, M., and Butcher, E.C. (2007). The germinal center response is impaired in the absence of T cell-expressed CXCR5. Eur. J. Immunol. 37, 100-109 https://doi.org/10.1002/eji.200636486
  3. Ballesteros-Tato, A., Leon, B., Graf, B.A., Moquin, A., Adams, P.S., Lund, F.E., and Randall, T.D. (2012). Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity 36, 847-856. https://doi.org/10.1016/j.immuni.2012.02.012
  4. Baumjohann, D., Okada, T., and Ansel, K.M. (2011). Cutting edge: distinct waves of BCL6 expression during T follicular helper cell development. J. Immunol. 187, 2089-2092. https://doi.org/10.4049/jimmunol.1101393
  5. Bentebibel, S.E., Lopez, S., Obermoser, G., Schmitt, N., Mueller, C., Harrod, C., Flano, E., Mejias, A., Albrecht, R.A., Blankenship, D., et al. (2013). Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci. Transl. Med. 5, 176ra32.
  6. Borriello, F., Sethna, M.P., Boyd, S.D., Schweitzer, A.N., Tivol, E.A., Jacoby, D., Strom, T.B., Simpson, E.M., Freeman, G.J., and Sharpe, A.H. (1997). B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity 6, 303-313. https://doi.org/10.1016/S1074-7613(00)80333-7
  7. Breitfeld, D., Ohl, L., Kremmer, E., Ellwart, J., Sallusto, F., Lipp, M., and Forster, 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. https://doi.org/10.1084/jem.192.11.1545
  8. Cannons, J.L., Qi, H., Lu, K.T., Dutta, M., Gomez-Rodriguez, J., Cheng, J., Wakeland, E.K., Germain, R.N., and Schwartzberg, P.L. (2010). Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 32, 253-265. https://doi.org/10.1016/j.immuni.2010.01.010
  9. Choi, Y.S., Kageyama, R., Eto, D., Escobar, T.C., Johnston, R.J., Monticelli, L., Lao, C., and Crotty, S. (2011a). ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 34, 932-946. https://doi.org/10.1016/j.immuni.2011.03.023
  10. Choi, Y.S., Kageyama, R., Eto, D., Escobar, T.C., Johnston, R.J., Monticelli, L., Lao, C., and Crotty, S. (2011b). ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 34, 932-946. https://doi.org/10.1016/j.immuni.2011.03.023
  11. Chtanova, T., Tangye, S.G., Newton, R., Frank, N., Hodge, M.R., Rolph, M.S., and Mackay, C.R. (2004). T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J. Immunol. 173, 68-78 https://doi.org/10.4049/jimmunol.173.1.68
  12. Crotty, S. (2014). T follicular helper cell differentiation, function, and roles in disease. Immunity 41, 529-542. https://doi.org/10.1016/j.immuni.2014.10.004
  13. Deenick, E.K., Chan, A., Ma, C.S., Gatto, D., Schwartzberg, P.L., Brink, R., and Tangye, S.G. (2010). Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling. Immunity 33, 241-253. https://doi.org/10.1016/j.immuni.2010.07.015
  14. Fahey, L.M., Wilson, E.B., Elsaesser, H., Fistonich, C.D., McGavern, D.B., and Brooks, D.G. (2011). Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells. J. Exp. Med. 208, 987-999 https://doi.org/10.1084/jem.20101773
  15. Fazilleau, N., Eisenbraun, M.D., Malherbe, L., Ebright, J.N., Pogue-Caley, R.R., Heyzer-Williams, L.J., and Heyzer-Williams, M.G. (2007). Lymphoid reservoirs of antigen-specific memory T helper cells. Nat. Immunol. 8, 753-761.
  16. Fazilleau, N., Heyzer-Williams, L.J., Rosen, H., and Heyzer-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. https://doi.org/10.1038/ni.1704
  17. Ferguson, S.E., Han, S., Kelsoe, G., and Thompson, C.B. (1996). CD28 is required for germinal center formation. J. Immunol. 156, 4576-81.
  18. Gigoux, M., Shang, J., Pak, Y., Xu, M., Choe, J., Mak, T.W., and Suh, W.K. (2009). Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase. Proc. Natl. Acad. Sci. USA 106, 20371-20376. https://doi.org/10.1073/pnas.0911573106
  19. Gigoux, M., Lovato, A., Leconte, J., Leung, J., Sonenberg, N., and Suh, W.K. (2014). Inducible costimulator facilitates T-dependent B cell activation by augmenting IL-4 translation. Mol. Immunol. 59, 46-54. https://doi.org/10.1016/j.molimm.2014.01.008
  20. Goenka, R., Barnett, L.G., Silver, J.S., O'Neill, P.J., Hunter, C.A., Cancro, M.P., and Laufer, T.M. (2011). Cutting edge: dendritic cell-restricted antigen presentation initiates the follicular helper T cell program but cannot complete ultimate effector differentiation. J. Immunol. 187, 1091-1095. https://doi.org/10.4049/jimmunol.1100853
  21. Good-Jacobson, K.L., Song, E., Anderson, S., Sharpe, A.H., and Shlomchik, M.J. (2012). CD80 expression on B cells regulates murine T follicular helper development, germinal center B cell survival, and plasma cell generation. J. Immunol. 188, 4217-4225. https://doi.org/10.4049/jimmunol.1102885
  22. Haynes, N.M., Allen, C.D., Lesley, R., Ansel, K.M., Killeen, N., and Cyster, J.G. (2007). Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J. Immunol. 179, 5099-5108 https://doi.org/10.4049/jimmunol.179.8.5099
  23. He, J., Tsai, L.M., Leong, Y.A., Hu, X., Ma, C.S., Chevalier, N., Sun, X., Vandenberg, K., Rockman, S., Ding, Y., et al. (2013). Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. Immunity 39, 770-781. https://doi.org/10.1016/j.immuni.2013.09.007
  24. 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. https://doi.org/10.1126/science.1175870
  25. Johnston, R.J., Choi, Y.S., Diamond, J.A., Yang, J.A., and Crotty, S. (2012). STAT5 is a potent negative regulator of TFH cell differentiation. J. Exp. Med. 209, 243-250. https://doi.org/10.1084/jem.20111174
  26. Junt, T., Fink, K., Forster, R., Senn, B., Lipp, M., Muramatsu, M., Zinkernagel, R.M., Ludewig, B., and Hengartner, H. (2005). CXCR5-dependent seeding of follicular niches by B and Th cells augments antiviral B cell responses. J. Immunol. 175, 7109-7116. https://doi.org/10.4049/jimmunol.175.11.7109
  27. Kaji, T., Ishige, A., Hikida, M., Taka, J., Hijikata, A., Kubo, M., Nagashima, T., Takahashi, Y., Kurosaki, T., Okada, M., et al. (2012). Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J. Exp. Med. 209, 2079-2097 https://doi.org/10.1084/jem.20120127
  28. Kaji, T., Furukawa, K., Ishige, A., Toyokura, I., Nomura, M., Okada, M., Takahashi, Y., Shimoda, M., and Takemori, T. (2013). Both mutated and unmutated memory B cells accumulate mutations in the course of the secondary response and develop a new antibody repertoire optimally adapted to the secondary stimulus. Int. Immunol. 25, 683-695. https://doi.org/10.1093/intimm/dxt030
  29. Kang, S.G., Liu, W.H., Lu, P., Jin, H.Y., Lim, H.W., Shepherd, J., Fremgen, D., Verdin, E., Oldstone, M.B., Qi, H., et al. (2013). MicroRNAs of the miR-17 approximately 92 family are critical regulators of T(FH) differentiation. Nat. Immunol. 14, 849-857 https://doi.org/10.1038/ni.2648
  30. Kim, C.H., Rott, L.S., Clark-Lewis, I., Campbell, D.J., Wu, L., and Butcher, E.C. (2001). Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J. Exp. Med. 193, 1373-1381. https://doi.org/10.1084/jem.193.12.1373
  31. Kim, C.H., Lim, H.W., Kim, J.R., Rott, L., Hillsamer, P., and Butcher, E.C. (2004). Unique gene expression program of human germinal center T helper cells. Blood 104, 1952-1960. https://doi.org/10.1182/blood-2004-03-1206
  32. 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 https://doi.org/10.1084/jem.20090313
  33. Kuppers, R., Zhao, M., Hansmann, M.L., and Rajewsky, K. (1993). Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J. 12, 4955-4967
  34. Leon, B., Bradley, J.E., Lund, F.E., Randall, T.D., and Ballesteros-Tato, A. (2014). FoxP3+ regulatory T cells promote influenzaspecific Tfh responses by controlling IL-2 availability. Nat. Commun. 5, 3495.
  35. Liang, L., Porter, E.M., and Sha, W.C. (2002). Constitutive expression of the B7h ligand for inducible costimulator on naive B cells is extinguished after activation by distinct B cell receptor and interleukin 4 receptor-mediated pathways and can be rescued by CD40 signaling. J. Exp. Med. 196, 97-108 https://doi.org/10.1084/jem.20020298
  36. Linterman, M.A., Rigby, R.J., Wong, R., Silva, D., Withers, D., Anderson, G., Verma, N.K., Brink, R., Hutloff, A., Goodnow, C.C., et al. (2009). Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS. Immunity 30, 228-241. https://doi.org/10.1016/j.immuni.2008.12.015
  37. Liu, Y.J., Zhang, J., Lane, P.J., Chan, E.Y., and MacLennan, I.C. (1991). Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cellindependent antigens. Eur. J. Immunol. 21, 2951-2962. https://doi.org/10.1002/eji.1830211209
  38. Liu, X., Yan, X., Zhong, B., Nurieva, R.I., Wang, A., Wang, X., Martin-Orozco, N., Wang, Y., Chang, S.H., Esplugues, E., et al. (2012). Bcl6 expression specifies the T follicular helper cell program in vivo. J. Exp. Med. 209, 1841-1824. https://doi.org/10.1084/jem.20120219
  39. Liu, X., Nurieva, R.I., and Dong, C. (2013). Transcriptional regulation of follicular T-helper (Tfh) cells. Immunol. Rev. 252, 139-145. https://doi.org/10.1111/imr.12040
  40. Liu, D., Xu, H., Shih, C., Wan, Z., Ma, X., Ma, W., Luo, D., and Qi, H. (2014a). T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction. Nature [Epub ahead of print].
  41. Liu, X., Chen, X., Zhong, B., Wang, A., Wang, X., Chu, F., Nurieva, R.I., Yan, X., Chen, P., van der Flier, L.G., et al. (2014b). Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature 507, 513-518 https://doi.org/10.1038/nature12910
  42. Lo, C.G., Xu, Y., Proia, R.L., and Cyster, J.G. (2005). Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit. J. Exp. Med. 201, 291-301. https://doi.org/10.1084/jem.20041509
  43. Locci, M., Havenar-Daughton, C., Landais, E., Wu, J., Kroenke, M.A., Arlehamn, C.L., Su, L.F., Cubas, R., Davis, M.M., Sette, A., et al. (2013). Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity 39, 758-769 https://doi.org/10.1016/j.immuni.2013.08.031
  44. Logue, E.C., Bakkour, S., Murphy, M.M., Nolla, H., and Sha, W.C. (2006). ICOS-induced B7h shedding on B cells is inhibited by TLR7/8 and TLR9. J. Immunol. 177, 2356-2364. https://doi.org/10.4049/jimmunol.177.4.2356
  45. Luthje, K., Kallies, A., Shimohakamada, Y., Belz, G.T., Light, A., Tarlinton, D.M., and Nutt, S.L. (2012). The development and fate of follicular helper T cells defined by an IL-21 reporter mouse. Nat. Immunol. 13, 491-498 https://doi.org/10.1038/ni.2261
  46. McAdam, A.J., Chang, T.T., Lumelsky, A.E., Greenfield, E.A., Boussiotis, V.A., Duke-Cohan, J.S., Chernova, T., Malenkovich, N., Jabs, C., Kuchroo, V.K., et al. (2000). Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J. Immunol. 165, 5035-5040. https://doi.org/10.4049/jimmunol.165.9.5035
  47. Morita, R., Schmitt, N., Bentebibel, S.E., Ranganathan, R., Bourdery, L., Zurawski, G., Foucat, E., Dullaers, M., Oh, S., Sabzghabaei, N., et al. (2011). Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34, 108-121. https://doi.org/10.1016/j.immuni.2010.12.012
  48. Moriyama, S., Takahashi, N., Green, J.A., Hori, S., Kubo, M., Cyster, J.G., and Okada, T. (2014). Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers. J. Exp. Med. 211, 1297-1305. https://doi.org/10.1084/jem.20131666
  49. Nakayamada, S., Kanno, Y., Takahashi, H., Jankovic, D., Lu, K.T., Johnson, T.A., Sun, H.W., Vahedi, G., Hakim, O., Handon, R., et al. (2011). Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 35, 919-931. https://doi.org/10.1016/j.immuni.2011.11.012
  50. Nakayamada, S., Takahashi, H., Kanno, Y., and O'Shea, J.J. (2012). Helper T cell diversity and plasticity. Curr. Opin. Immunol. 24, 297-302. https://doi.org/10.1016/j.coi.2012.01.014
  51. Nurieva, R.I., Chuvpilo, S., Wieder, E.D., Elkon, K.B., Locksley, R., Serfling, E., and Dong, C. (2007). A costimulation-initiated signaling pathway regulates NFATc1 transcription in T lymphocytes. J. Immunol. 179, 1096-1103. https://doi.org/10.4049/jimmunol.179.2.1096
  52. 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., et al. (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 https://doi.org/10.1016/j.immuni.2008.05.009
  53. 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. https://doi.org/10.1126/science.1176676
  54. Nurieva, R.I., Podd, A., Chen, Y., Alekseev, A.M., Yu, M., Qi, X., Huang, H., Wen, R., Wang, J., Li, H.S., et al. (2012). STAT5 protein negatively regulates T follicular helper (Tfh) cell generation and function. J. Biol. Chem. 287, 11234-11239 https://doi.org/10.1074/jbc.M111.324046
  55. Oracki, S.A., Walker, J.A., Hibbs, M.L., Corcoran, L.M., and Tarlinton, D.M. (2010). Plasma cell development and survival. Immunol. Rev. 237, 140-159 https://doi.org/10.1111/j.1600-065X.2010.00940.x
  56. Pratama, A., and Vinuesa, C.G. (2014). Control of TFH cell numbers: why and how? Immunol. Cell Biol. 92, 40-48 https://doi.org/10.1038/icb.2013.69
  57. Qi, H., Cannons, J.L., Klauschen, F., Schwartzberg, P.L., and Germain, R.N. (2008). SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455, 764-769 https://doi.org/10.1038/nature07345
  58. Rasheed, A.U., Rahn, H.P., Sallusto, F., Lipp, M., and Muller, G. (2006). Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression. Eur. J. Immunol. 36, 1892-1903. https://doi.org/10.1002/eji.200636136
  59. Reinhardt, R.L., Liang, H.E., and Locksley, R.M. (2009). Cytokinesecreting follicular T cells shape the antibody repertoire. Nat. Immunol. 10, 385-393.
  60. Rolf, J., Bell, S.E., Kovesdi, D., Janas, M.L., Soond, D.R., Webb, L.M., Santinelli, S., Saunders, T., Hebeis, B., Killeen, N., et al. (2010). Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction. J. Immunol. 185, 4042-4052. https://doi.org/10.4049/jimmunol.1001730
  61. Salek-Ardakani, S., Choi, Y.S., Rafii-El-Idrissi, B.M., Flynn, R., Arens, R., Shoenberger, S., Crotty, S., Croft, M., and Salek-Ardakani, S. (2011). B cell-specific expression of B7-2 is required for follicular Th cell function in response to vaccinia virus. J. Immunol. 186, 5294-5303. https://doi.org/10.4049/jimmunol.1100406
  62. 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. https://doi.org/10.1084/jem.192.11.1553
  63. Schmitt, N., Morita, R., Bourdery, L., Bentebibel, S.E., Zurawski, S.M., Banchereau, J., and Ueno, H. (2009). Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity 31, 158-169 https://doi.org/10.1016/j.immuni.2009.04.016
  64. Schwartzberg, P.L., Mueller, K.L., Qi, H., and Cannons, J.L. (2009). SLAM receptors and SAP influence lymphocyte interactions, development and function. Nat. Rev. Immunol. 9, 39-46. https://doi.org/10.1038/nri2456
  65. Shlomchik, M.J., and Weisel, F. (2012). Germinal center selection and the development of memory B and plasma cells. Immunol. Rev. 247, 52-63. https://doi.org/10.1111/j.1600-065X.2012.01124.x
  66. Shulman, Z., Gitlin, A.D., Targ, S., Jankovic, M., Pasqual, G., Nussenzweig, M.C., and Victora, G.D. (2013). T follicular helper cell dynamics in germinal centers. Science 341, 673-677 https://doi.org/10.1126/science.1241680
  67. Shulman, Z., Gitlin, A.D., Weinstein, J.S., Lainez, B., Esplugues, E., Flavell, R.A., Craft, J.E., and Nussenzweig, M.C. (2014). Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 345, 1058-1062. https://doi.org/10.1126/science.1257861
  68. Suh, W.K., Tafuri, A., Berg-Brown, N.N., Shahinian, A., Plyte, S., Duncan, G.S., Okada, H., Wakeham, A., Odermatt, B., Ohashi, P.S., et al. (2004). The inducible costimulator plays the major costimulatory role in humoral immune responses in the absence of CD28. J. Immunol. 172, 5917-5923. https://doi.org/10.4049/jimmunol.172.10.5917
  69. Sweet, R.A., Lee, S.K., and Vinuesa, C.G. (2012). Developing connections amongst key cytokines and dysregulated germinal centers in autoimmunity. Curr. Opin. Immunol. 24, 658-664. https://doi.org/10.1016/j.coi.2012.10.003
  70. Tubo, N.J., Pagan, A.J., Taylor, J.J., Nelson, R.W., Linehan, J.L., Ertelt, J.M., Huseby, E.S., Way, S.S., and Jenkins, M.K. (2013). Single naive CD4+ T cells from a diverse repertoire produce different effector cell types during infection. Cell 153, 785-796. https://doi.org/10.1016/j.cell.2013.04.007
  71. Victora, G.D., and Nussenzweig, M.C. (2012). Germinal centers. Annu. Rev. Immunol. 30, 429-457 https://doi.org/10.1146/annurev-immunol-020711-075032
  72. Victora, G.D., Schwickert, T.A., Fooksman, D.R., Kamphorst, A.O., Meyer-Hermann, M., Dustin, M.L., and Nussenzweig, M.C. (2010). Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592-605. https://doi.org/10.1016/j.cell.2010.10.032
  73. Walker, L.S., Gulbranson-Judge, A., Flynn, S., Brocker, T., Raykundalia, C., Goodall, M., Forster, R., Lipp, M., and Lane, P. (1999). Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. J. Exp. Med. 190, 1115-1122. https://doi.org/10.1084/jem.190.8.1115
  74. Walker, L.S., Wiggett, H.E., Gaspal, F.M., Raykundalia, C.R., Goodall, M.D., Toellner, K.M., and Lane, P.J. (2003). Established T cell-driven germinal center B cell proliferation is independent of CD28 signaling but is tightly regulated through CTLA-4. J. Immunol. 170, 91-98 https://doi.org/10.4049/jimmunol.170.1.91
  75. Watanabe, M., Takagi, Y., Kotani, M., Hara, Y., Inamine, A., Hayashi, K., Ogawa, S., Takeda, K., Tanabe, K., and Abe, R. (2008). Down-regulation of ICOS ligand by interaction with ICOS functions as a regulatory mechanism for immune responses. J. Immunol. 180, 5222-5234. https://doi.org/10.4049/jimmunol.180.8.5222
  76. Xu, H., Li, X., Liu, D., Li, J., Zhang, X., Chen, X., Hou, S., Peng, L., Xu, C., Liu, W., et al. (2013). Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility. Nature 496, 523-527 https://doi.org/10.1038/nature12058
  77. Yu, D., Rao, S., Tsai, L.M., Lee, S.K., He, Y., Sutcliffe, E.L., Srivastava, M., Linterman, M., Zheng, L., Simpson, N., et al. (2009). The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457-468 https://doi.org/10.1016/j.immuni.2009.07.002
  78. 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 https://doi.org/10.1084/jem.20090303
  79. Zuccarino-Catania, G.V., Sadanand, S., Weisel, F.J., Tomayko, M.M., Meng, H., Kleinstein, S.H., Good-Jacobson, K.L., and Shlomchik, M.J. (2014). CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype. Nat. Immunol. 15, 631-637

Cited by

  1. Selective pre-priming of HA-specific CD4 T cells restores immunological reactivity to HA on heterosubtypic influenza infection vol.12, pp.5, 2017, https://doi.org/10.1371/journal.pone.0176407
  2. Vaccine Induction of Lymph Node–Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques vol.196, pp.4, 2016, https://doi.org/10.4049/jimmunol.1502137
  3. Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases vol.22, pp.5, 2016, https://doi.org/10.1097/MIB.0000000000000714
  4. The Role of CD4 T Cell Memory in Generating Protective Immunity to Novel and Potentially Pandemic Strains of Influenza vol.7, 2016, https://doi.org/10.3389/fimmu.2016.00010
  5. Adaptive immunity in the liver vol.13, pp.3, 2016, https://doi.org/10.1038/cmi.2016.4
  6. Follicular helper T cell in immunity and autoimmunity vol.49, pp.5, 2016, https://doi.org/10.1590/1414-431X20165209
  7. Activated T follicular helper-like cells are released into blood after oral vaccination and correlate with vaccine specific mucosal B-cell memory vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-20740-3
  8. T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target pp.1437-7799, 2019, https://doi.org/10.1007/s10157-018-1665-0
  9. T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response pp.2164-554X, 2018, https://doi.org/10.1080/21645515.2018.1495303
  10. The Intricate Link among Gut “Immunological Niche,” Microbiota, and Xenobiotics in Intestinal Pathology vol.2017, pp.None, 2015, https://doi.org/10.1155/2017/8390595
  11. ICOS Signaling Controls Induction and Maintenance of Collagen-Induced Arthritis vol.200, pp.9, 2018, https://doi.org/10.4049/jimmunol.1701305
  12. Unique Phenotypes and Functions of Follicular Helper T Cells and Regulatory T Cells in Sjögren’s Syndrome vol.14, pp.3, 2015, https://doi.org/10.2174/1573397113666170125122858