Abstract
Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, hightiter IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment.
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Hesselmar, B., Aberg, N., Aberg, B., Eriksson, B., and Bjorksten, B. (1999), Clin Exp Allergy 29, 611–617.
Braback, L., Kjellman, N.I., Sandin, A., and Bjorksten, B. (2001), Pediatr Allergy Immunol 12, 4–10.
Svanes, C., Jarvis, D., Chinn, S., and Burney, P. (1999), J Allergy Clin Immunol 103, 415–420.
Roost, H.P., Kunzli, N., Schindler, C., et al. (1999), J Allergy Clin, Immunol 104, 941–947.
Sporik, R., Squillace, S.P., Ingram, J.M., Rakes, G., Honsinger, R.W., and Platts-Mills, T.A. (1999), Thorax 54, 675–680.
Platts-Mills, T., Vaughan, J., Squillace, S., Woodfolk, J., and Sporik, R. (2001), Lancet 357, 752–756.
Holscher, B., Frye, C., Wichmann, H.E., and Heinrich, J. (2002), Pediatr Allergy Immunol 13, 334–341.
Linneberg, A., Nielsen, N.H., Madsen, F., Frolund, L., Dirksen, A., and Jorgensen, T. (2003), Allergy 58, 21–26.
Kuehr, J., Frischer, T., Karmaus, W., et al. (1992), J Allergy Clin Immunol 90, 358–363.
Wahn, U., Lau, S., Bergmann, R., et al. (1997), J Allergy Clin Immunol 99, 763–769.
Suoniemi, I., Bjorksten, F., Haahtela, T. (1981), Allergy 36, 263–268.
Arshad, S.H. (1991), Br J Clin Pract 45, 88, 89.
Custovic, A., Simpson, B.M., Simpson, A., Kissen, P., and Woodcock, A. (2001), Lancet 358, 188–193.
Lindfors, A., Wickman, M., Hedlin, G., Pershagen, G., Rietz, H., and Nordvall, S.L. (1995), Arch Dis Child 73, 408–412.
Melen, E., Wickman, M., Nordvall, S.L., van Hage-Hamsten, M., and Lindfors, A. (2001), Allergy 56, 646–652.
Almqvist, C., Egmar, A.C., Hedlin, G., et al. (2003), Clin Exp Allergy 33, 1190–1197.
Hesselmar, B., Aberg, B., Eriksson, B., Bjorksten, B., and Aberg, N. (2003), Clin Exp Allergy 33, 1681–1685.
Perzanowski, M., Ronmark, E., Platts-Mills, T.A., and Lundback, B. (2002), Am J Respir Crit Care Med 166, 696–702.
Custovic, A., Wimpson, B.M., Simpson, A., et al. (2003), J Allergy Clin Immunol 111, 402–407.
Ownby, D.R., Johnson, C., and Peterson, E.L. (2002) JAMA 288, 963–972.
Ingram, J.M., Sporik, R., Rose, G., Honsinger, R., Chapman, M.D., and Platts-Mills T.A.E. (1995), J Allergy Clin Immunol 96, 449–456.
Custovic, A., Simpson, B., Simpson, A., Hallam, C., Craven, M., and Woodcock, A. (1999), Allergy 54, 612–616.
Custovic, A., Simpson, A., Padhi, H., Green, R.M., Chapman, M.D., and Woodcock, A. (1998), Thorax 53, 33–38.
DeLucca, S.D., O’Meara, T.J., and Tovey, E.R. (2000), J Allergy Clin Immunol 106, 874–879.
Luczynska, C.M., Li, Y., Chapman, M.D., and Platts-Mills T.A.E. (1990), Am Rev Respir Dis 141, 361–367.
DeBlay, F., Heymann, P.W., Chapman, M.D., and Platts-Mills, T.A.E. (1991), J Allergy Clin Immunol 88, 919–926.
Lambrecht, B.N. and Hammad, H. (2003), Nat Rev Immunol 3, 994–1003.
Eisenbarth, S.C., Piggott, D.A., Huleatt, J.W., Visintin, I., Herrick, C.A., and Bottomly, K. (2002), J Exp Med 196, 1645–1651.
Halapi, E. and Hakonarson, H. (2004), Curr Opin Pulm Med 10, 22–30.
Ebner, C., Siemann, U., Bohle, B., et al. (1997), Clin Exp Allergy 27, 1007–1015.
Akdis, C.A., Blesken, T., Akdis, M., Wuthrich, B., and Blaser, K. (1998), J Clin Invest 102, 98–106.
Bellinghausen, I., Metz, G., Enk, A.H., Christmann, S., Knop, J., and Saloga, J. (1997) Eur J Immunol 27, 1131–1139.
Oldfield, W.L., Kay, A.B., and Larche, M. (2001), J Immunol 167, 1734–1739.
Akdis, C.A. and Blaser, K. (1999), FASEB 13, 603–609.
Oldfield, W.L.G., Stillion, R., Kay, A.B., and Larche, M. (2002), J Allergy Clin Immunol 109, S261. (Abstr.).
Carneiro, R., Reefer, A., Wilson, B., et al. (2004), J Invest Dermatol 122, 927–936.
Akdis, C.A., Joss, A., Akdis, M., Faith, A., and Blaser, K. (2000), FASEB 14, 1666–1668
Jutel, M., Pichler, W.J., Skrvic, D., Urwyler, A., Dahinden, C., and Muller, U.R. (1995), J Immunol 154, 4187–4194.
Meissner, N., Kochs, S., Coutelle, J., et al. (1999), Clin Exp Allergy 29, 618–625.
Oda, N., Yamashita, N., Minoguchi, K., Rakeno, M., Kaneko, S., and Adachi, M. (1998), Cell Immunol 190, 43–50.
Secrist, H., Chelen, C.J., Wen, Y., Marshall, J.D., and Umetsu, D.T. (1993), J Exp Med 178, 2123–2130.
Hamid, Q.A., Schotman, E., Jacobson, M.R., Walker, S.M., and Durham, S.R. (1997) J Allergy Clin Immunol 99, 254–260.
Reefer, A.J., Carneiro, R.M., Custis, N.J., et al. (2004), J Immunol 172, 2763–2772.
Francis, J.N., Till, S.J., and Durham, S.R. (2003), J Allergy Clin Immunol 111, 1255–1261.
Ewbank, P.A., Murray, J., Sanders, K., Curran-Everett, D., Dreskin, S., and Nelson, H.S. (2003), J Allergy Clin Immunol 111, 155–161.
O’Brien, R.M., Byron, K.A., Varigos, G.A., and Thomas, W.R. (1997), Clin Exp Allergy 27, 46–51.
Moverare, R., Elfman, L., Bjornsson, E., and Stalenhiem, G. (2000), Immunol Lett 3, 51–56.
Nouri-Aria, K.T., Wacholz, P.A., Francis, J.N., et al. (2004), J Immunol 172, 3252–3259.
Oldfield, W.L., Larche, M., and Kay, A.B. (2002), Lancet 360, 47–53.
Ohman, J.L., Findlay, S.R., and Leitermann, K.M. (1984), J Allergy Clin Immunol 74, 230–239.
Aalberse, R.C., van der Gaag, R., and van Leuwen, J. (1983), J Immunol 130, 722–726.
Djurup, R. and Osterballe, O. (1984), Allergy 39, 433–441.
Durham, S.R., Kay, A.B., and Hamid, Q. (1995), Int Arch Allergy Immunol 107, 282–284.
Akbari, O., DeKruyff, R.H., and Umetsu, D.T. (2001), Nat Immunol 2, 725–731.
Hansen, G., McIntire, J.J., Yeung, V.P., et al. (2000), J Clin Invest 105, 61–70.
Oh, J.W., Seroogy, C.M., Meyer, E.H., et al. (2002), J Allergy Clin Immunol 110, 460–468.
Chen, Y., Kuchroo, V.K., Inobe, J., Hafler, D.A., and Weiner, H.L. (1994), Science 265, 1237–1240.
Prud’homme, G.J. and Piccirillo, C.A. (2000), J Autoimmun 14, 23–42.
Groux, H., O’Garra, A., Bigler, M., et al. (1997), Nature 389, 737–742.
Cottrez, F., Hurst, S.D., Coffman, R.L., and Groux, H. (2000), J Immunol 165, 4848–4853.
Powrie, F., Read, S., Mottet, C., Uhlig, H., and Maloy, K. (2003), Novartis Found Symp 252, 92–98.
Levings, M.K., Sangregorio, R., Sartirana, C., et al. (2002), J Exp Med 196, 1335–1346.
Levings, M.K., Bacchetta, R., Schulz, U., and Roncarolo, M.G. (2002), Int Arch Allergy Immunol 129, 263–276.
Chen, W., Jin, W., Hardegen, N., et al. (2003), J Exp Med 198, 1875–1886.
Fantini, M.C., Becker, C., Monteleone, G., Pallone, F., Galle, P.R., and Neurath, M.F. (2004), J Immunol 172, 5149–5153.
Ling, E.M., Smith, T., Nguyen, X.D., et al. (2004), Lancet 363, 608–615.
Wacholz, P.A., Soni, N.K., Till, S.J. (2003), J Allergy Clin Immunol 112, 915–922.
van Neerven, R.J.J., Wikborg, T., Lund, G., et al. (1999) J Immunol 163, 2944–2952.
Jeannin, P., Lecoanet, S., Delneste, Y., Gauchat, J-F., and Bonnefoy, J-Y. (1998) J Immunol 160, 3555–3561.
Boyton, R.J., Zaccai, N., Jones, E.Y., and Altmann, D.M. (2002), J Immunol 168, 1018–1027.
Pfeiffer, C., Stein, J., Southwood, S., Ketelaar, H., Sette, A., and Bottomly, K. (1995), J Exp Med 181, 1569–1574.
Nicholson, L.B., Greer, J.M., Sobel, R.A., Lees, M.B., and Kuchroo, V.K. (1995), Immunity 3, 397–405.
Woodfolk, J.A., Sung, S.S., Benjamin, D.C., Lee, J.K., and Platts-Mills, T.A. (2000), J Immunol 165, 4379–4387.
Bocek, P., Foucras, G.L., and Paul, W.E. (2004), J Exp Med 199, 1619–1630.
Erwin, E.A., Wickens, K., Custis, N.J., et al. (2005), J Allergy Clin Immunol 115, 74–79.
Ou, L-S., Golevan, E., Hall, C., and Leung, D.Y.M. (2004), J Allergy Clin Immunol 113, 756–763.
Gereda, J.E., Leung, D.Y., Thatayatikom, A., et al. (2000), Lancet, 13, 1680–1683.
von Mutius, E., Braun-Fahrlander, C., Schierl, R., et al. (2000), Clin Exp Allergy 30, 1230–1234.
Ormstad, H., Groeng, E.C., Duffort, O., and Lovik, M. (2003), Toxicology 188, 309–318.
Bolte, G., Bischof, W., Borte, M., Lehmann, I., Wichmann, H.E., Heinrich, J., LISA Study Group. (2003), Clin Exp Allergy 33, 770–776.
Custis, N.J., Woodfolk, J., and Platts-Mills, T. (2004), J Allergy Clin Immunol 113, S259 (Abstr.).
Kaiser, L., Gronlund, H., Sandalova, T., et al. (2003), J Biol Chem 278, 37,730–37,735.
Wang, S.Z., Rosenberger, C.L., Bao Y.X., Stark, J.M., and Harrod, K.S. (2003), J Immunol 171, 1051–1060.
Dierynck, I., Bernard, A., Roels, H., and De Ley, M. (1996), Mult Scler 1, 385–387.
Singh, G. and Katyal, S.L. (1997), Am J Respir Cell Mol Biol 17, 141–143.
Celedon, J.C., Litonjua, A.A., Ryan, L., Platts-Mills, T., Weiss, S.T., and Gold, D.R. (2002), Lancet 360, 781,782.
Nafstad, P., Magnus, P., Gaarder, P.I., and Jaakkola, J.J. (2001), Allergy 56, 307–312.
Oryszczyn, M.P., Annesi-Maesano, I., Charpin, D., and Kauffman, F. (2003), Allergy 58, 1136–1143.
Counsell, C.M., Bond, J.F. Ohman, J.L., Greenstein, J.L., and Garman, R.D. (1996), J Allergy Clin Immunol 98, 884–894
Mark, P.G., Segal, D.B. Dallaire, M.L., and Garman, R.D. (1996), Clin Exp Allergy 26, 1316–1328
Maguire, P., Nicodemus, C., Robinson, D., Aaronson, D., and Umetsu, D.T. (1999), Clin Immunol 93, 222–231.
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Woodfolk, J.A. High-dose allergen exposure leads to tolerance. Clinic Rev Allerg Immunol 28, 43–58 (2005). https://doi.org/10.1385/CRIAI:28:1:043
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DOI: https://doi.org/10.1385/CRIAI:28:1:043