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Erschienen in: Current Allergy and Asthma Reports 4/2017

01.04.2017 | Immunotherapy and Immunomodulators (B Vickery, Section Editor)

Human Immune Monitoring Techniques during Food Allergen Immunotherapy

verfasst von: Blake Rust, Erik Wambre

Erschienen in: Current Allergy and Asthma Reports | Ausgabe 4/2017

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Abstract

Purpose of Review

Encouraging results from recent food allergen immunotherapy clinical trials indicate that the immune system plays an essential role in peripheral tolerance to food allergen. Thus, the monitoring of changes in immune responses and their possible correlation with clinical outcome in allergic patients receiving immunotherapies could theoretically serve as surrogate markers and be harnessed as rationale for food allergen immunotherapy development.

Recent Findings

A shift towards antigen specificity in recent assays has provided a solid foundation for the elucidation of cellular mechanisms involved in food allergen immunotherapy as well as the tracking of allergen-specific immune cells.

Summary

In this review, we overview the current challenges and technologies used in immune monitoring during immunotherapy in allergic patients with a focus on cell-mediated immunity. We also discuss critical steps involved in some of the cellular immune assays utilized in clinical trials.
Literatur
1.
Zurück zum Zitat Peters RL, Gurrin LC, Allen KJ. The predictive value of skin prick testing for challenge-proven food allergy: a systematic review. Pediatr Allergy Immunol. 2012;23:347–52.CrossRefPubMed Peters RL, Gurrin LC, Allen KJ. The predictive value of skin prick testing for challenge-proven food allergy: a systematic review. Pediatr Allergy Immunol. 2012;23:347–52.CrossRefPubMed
2.
Zurück zum Zitat Kutscher S, et al. Overnight resting of PBMC changes functional signatures of antigen specific T- cell responses: impact for immune monitoring within clinical trials. PLoS One. 2013;8:e76215.CrossRefPubMedPubMedCentral Kutscher S, et al. Overnight resting of PBMC changes functional signatures of antigen specific T- cell responses: impact for immune monitoring within clinical trials. PLoS One. 2013;8:e76215.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Lao-Araya M, Steveling E, Scadding GW, Durham SR, Shamji MH. Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2014;134:1193–1195.e4.CrossRefPubMed Lao-Araya M, Steveling E, Scadding GW, Durham SR, Shamji MH. Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2014;134:1193–1195.e4.CrossRefPubMed
5.
Zurück zum Zitat Bonvalet M, et al. Allergen-specific CD4 + T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy. Clin Exp Allergy. 2012;42:1745–55.CrossRefPubMed Bonvalet M, et al. Allergen-specific CD4 + T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy. Clin Exp Allergy. 2012;42:1745–55.CrossRefPubMed
6.
Zurück zum Zitat Schroeder JT, MacGlashan DW, Lichtenstein LM. Human basophils: mediator release and cytokine production. Adv Immunol. 2001;77:93–122.CrossRefPubMed Schroeder JT, MacGlashan DW, Lichtenstein LM. Human basophils: mediator release and cytokine production. Adv Immunol. 2001;77:93–122.CrossRefPubMed
7.
Zurück zum Zitat Kleine-Tebbe J, et al. Diagnostic tests based on human basophils: potentials, pitfalls and perspectives. Int Arch Allergy Immunol. 2006;141:79–90.CrossRefPubMed Kleine-Tebbe J, et al. Diagnostic tests based on human basophils: potentials, pitfalls and perspectives. Int Arch Allergy Immunol. 2006;141:79–90.CrossRefPubMed
8.
Zurück zum Zitat Ebo DG, et al. Basophil activation test by flow cytometry: present and future applications in allergology. Cytom Part B Clin Cytom. 2008;74B:201–10.CrossRef Ebo DG, et al. Basophil activation test by flow cytometry: present and future applications in allergology. Cytom Part B Clin Cytom. 2008;74B:201–10.CrossRef
9.
Zurück zum Zitat Thyagarajan A, et al. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children. Clin Exp Allergy. 2012;42:1197–205.CrossRefPubMedPubMedCentral Thyagarajan A, et al. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children. Clin Exp Allergy. 2012;42:1197–205.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Gernez Y, Waters J, Tirouvanziam R, Herzenberg L, Moss R. Basophil activation test determination of CD63 combined with CD203c is not superior to CD203c alone in identifying allergic bronchopulmonary aspergillosis in cystic fibrosis. J Allergy Clin Immunol. 2016;138:1195–6.CrossRefPubMed Gernez Y, Waters J, Tirouvanziam R, Herzenberg L, Moss R. Basophil activation test determination of CD63 combined with CD203c is not superior to CD203c alone in identifying allergic bronchopulmonary aspergillosis in cystic fibrosis. J Allergy Clin Immunol. 2016;138:1195–6.CrossRefPubMed
11.
Zurück zum Zitat Ishizaka K, Ishizaka T, Hornbrook MM. Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol. 1966;97:75–85.PubMed Ishizaka K, Ishizaka T, Hornbrook MM. Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol. 1966;97:75–85.PubMed
12.
Zurück zum Zitat Johansson SGO, Bennich H. Studies on a new class of immunoglobulin. I. Immunological properties. Nobel Symp 3. 1967;Almqvist a:193–7. Johansson SGO, Bennich H. Studies on a new class of immunoglobulin. I. Immunological properties. Nobel Symp 3. 1967;Almqvist a:193–7.
14.
15.
Zurück zum Zitat Dang TD, et al. Increasing the accuracy of peanut allergy diagnosis by using Ara h 2. J Allergy Clin Immunol. 2012;129:1056–63.CrossRefPubMed Dang TD, et al. Increasing the accuracy of peanut allergy diagnosis by using Ara h 2. J Allergy Clin Immunol. 2012;129:1056–63.CrossRefPubMed
16.
Zurück zum Zitat van de Veen W, et al. IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013;131:1204–12.CrossRefPubMed van de Veen W, et al. IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013;131:1204–12.CrossRefPubMed
17.
Zurück zum Zitat Boonpiyathad T, et al. High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers. Allergy. 2016; doi:10.1111/all.12966.PubMed Boonpiyathad T, et al. High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers. Allergy. 2016; doi:10.​1111/​all.​12966.PubMed
18.
Zurück zum Zitat Franz B, May KF, Dranoff G, Wucherpfennig K, Wucherpfennig K. Ex vivo characterization and isolation of rare memory B cells with antigen tetramers. Blood. 2011;118:348–57.CrossRefPubMedPubMedCentral Franz B, May KF, Dranoff G, Wucherpfennig K, Wucherpfennig K. Ex vivo characterization and isolation of rare memory B cells with antigen tetramers. Blood. 2011;118:348–57.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Hoh RA, et al. Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol. 2016;137:157–67.CrossRefPubMed Hoh RA, et al. Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol. 2016;137:157–67.CrossRefPubMed
20.
Zurück zum Zitat Turcanu V, Maleki SJ, Lack G. Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J Clin Invest. 2003;111:1065–72.CrossRefPubMedPubMedCentral Turcanu V, Maleki SJ, Lack G. Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J Clin Invest. 2003;111:1065–72.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Bedoret D, et al. Changes in antigen-specific T-cell number and function during oral desensitization in cow’s milk allergy enabled with omalizumab. Mucosal Immunol. 2012;5:267–76.CrossRefPubMedPubMedCentral Bedoret D, et al. Changes in antigen-specific T-cell number and function during oral desensitization in cow’s milk allergy enabled with omalizumab. Mucosal Immunol. 2012;5:267–76.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Scott-Taylor TH, Hourihane JB, Harper J, Strobel S. Patterns of food allergen-specific cytokine production by T lymphocytes of children with multiple allergies. Clin Exp Allergy. 2005;35:1473–80.CrossRefPubMed Scott-Taylor TH, Hourihane JB, Harper J, Strobel S. Patterns of food allergen-specific cytokine production by T lymphocytes of children with multiple allergies. Clin Exp Allergy. 2005;35:1473–80.CrossRefPubMed
23.
Zurück zum Zitat Schade RP, et al. Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow’s milk allergy: relevance of TH2 cytokines. J Allergy Clin Immunol. 2000;106:1155–62.CrossRefPubMed Schade RP, et al. Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow’s milk allergy: relevance of TH2 cytokines. J Allergy Clin Immunol. 2000;106:1155–62.CrossRefPubMed
24.
Zurück zum Zitat Wisniewski JA, et al. Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy. Clin Exp Allergy. 2015;45:1201–13.CrossRefPubMedPubMedCentral Wisniewski JA, et al. Analysis of cytokine production by peanut-reactive T cells identifies residual Th2 effectors in highly allergic children who received peanut oral immunotherapy. Clin Exp Allergy. 2015;45:1201–13.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Michaud B, et al. Casein-specific IL-4- and IL-13-secreting T cells: a tool to implement diagnosis of cow’s milk allergy. Allergy. 2014;69:1473–80.CrossRefPubMed Michaud B, et al. Casein-specific IL-4- and IL-13-secreting T cells: a tool to implement diagnosis of cow’s milk allergy. Allergy. 2014;69:1473–80.CrossRefPubMed
26.
Zurück zum Zitat • Nepom GT. MHC class II tetramers. J Immunol. 2012;188. In this excellent review, key issues governing CD4 T cell identification by MHC class II tetramers are discussed, and examples from human immune monitoring studies illustrate the lessons learned. • Nepom GT. MHC class II tetramers. J Immunol. 2012;188. In this excellent review, key issues governing CD4 T cell identification by MHC class II tetramers are discussed, and examples from human immune monitoring studies illustrate the lessons learned.
27.
Zurück zum Zitat Biselli R, Matricardi PM, D’Amelio R, Fattorossi A. Multiparametric flow cytometric analysis of the kinetics of surface molecule expression after polyclonal activation of human peripheral blood T lymphocytes. Scand J Immunol. 1992;35:439–47.CrossRefPubMed Biselli R, Matricardi PM, D’Amelio R, Fattorossi A. Multiparametric flow cytometric analysis of the kinetics of surface molecule expression after polyclonal activation of human peripheral blood T lymphocytes. Scand J Immunol. 1992;35:439–47.CrossRefPubMed
28.
Zurück zum Zitat • Chattopadhyay PK, Yu J, Roederer M. A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles. Nat Med. 2005;11:1113–7. An elegant study utilizing a live-cell assay to detect antigen-specific regulatory CD4+ T cell responses by CD154 expression. CrossRefPubMed • Chattopadhyay PK, Yu J, Roederer M. A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles. Nat Med. 2005;11:1113–7. An elegant study utilizing a live-cell assay to detect antigen-specific regulatory CD4+ T cell responses by CD154 expression. CrossRefPubMed
29.
Zurück zum Zitat Bacher P, et al. Antigen-reactive T cell enrichment for direct, high-resolution analysis of the human naive and memory Th cell repertoire. J Immunol. 2013;190:3967–76.CrossRefPubMed Bacher P, et al. Antigen-reactive T cell enrichment for direct, high-resolution analysis of the human naive and memory Th cell repertoire. J Immunol. 2013;190:3967–76.CrossRefPubMed
30.
Zurück zum Zitat Scriba TJ, et al. Ultrasensitive detection and phenotyping of CD4+ T cells with optimized HLA class II tetramer staining. J Immunol. 2005;175. Scriba TJ, et al. Ultrasensitive detection and phenotyping of CD4+ T cells with optimized HLA class II tetramer staining. J Immunol. 2005;175.
31.
Zurück zum Zitat • Wambre E, et al. Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy. J Allergy Clin Immunol. 2012;129:544–551.e7. This study used an ex-vivo tetramer approach to characterize allergen-specific CD4+ T cell responses at single level and showed that the differentiation stage divides these cells into two distinct subpopulations with unique functional properties and different fates during therapy. CrossRefPubMed • Wambre E, et al. Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy. J Allergy Clin Immunol. 2012;129:544–551.e7. This study used an ex-vivo tetramer approach to characterize allergen-specific CD4+ T cell responses at single level and showed that the differentiation stage divides these cells into two distinct subpopulations with unique functional properties and different fates during therapy. CrossRefPubMed
32.
Zurück zum Zitat Sandoval-Montes C, Santos-Argumedo L. CD38 is expressed selectively during the activation of a subset of mature T cells with reduced proliferation but improved potential to produce cytokines. J Leukoc Biol. 2004;77:513–21.CrossRefPubMed Sandoval-Montes C, Santos-Argumedo L. CD38 is expressed selectively during the activation of a subset of mature T cells with reduced proliferation but improved potential to produce cytokines. J Leukoc Biol. 2004;77:513–21.CrossRefPubMed
33.
34.
Zurück zum Zitat Kulis M, Vickery BP, Burks AW. Pioneering immunotherapy for food allergy: clinical outcomes and modulation of the immune response. Immunol Res. 2011;49:216–26.CrossRefPubMed Kulis M, Vickery BP, Burks AW. Pioneering immunotherapy for food allergy: clinical outcomes and modulation of the immune response. Immunol Res. 2011;49:216–26.CrossRefPubMed
35.
Zurück zum Zitat de Leeuw RJ, Kost SE, Kakal JA, Nelson BH. The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. Clin Cancer Res. 2012;18:3022–9.CrossRef de Leeuw RJ, Kost SE, Kakal JA, Nelson BH. The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. Clin Cancer Res. 2012;18:3022–9.CrossRef
36.
Zurück zum Zitat Devaud C, Darcy PK, Kershaw MH. Foxp3 expression in T regulatory cells and other cell lineages. Cancer Immunol Immunother. 2014;63:869–76.CrossRefPubMed Devaud C, Darcy PK, Kershaw MH. Foxp3 expression in T regulatory cells and other cell lineages. Cancer Immunol Immunother. 2014;63:869–76.CrossRefPubMed
37.
Zurück zum Zitat Abbas AK, et al. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 2013;14:307–8.CrossRefPubMed Abbas AK, et al. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 2013;14:307–8.CrossRefPubMed
38.
Zurück zum Zitat Syed A, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133:500–10.CrossRefPubMedPubMedCentral Syed A, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133:500–10.CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat •• Bacher P, et al. Regulatory T cell specificity directs tolerance versus allergy against aeroantigens in humans. Cell. 2016;17–24. An elegant study utilizing a live-cell assay to detect antigen-specific regulatory CD4+ T cell responses by CD137 expression. •• Bacher P, et al. Regulatory T cell specificity directs tolerance versus allergy against aeroantigens in humans. Cell. 2016;17–24. An elegant study utilizing a live-cell assay to detect antigen-specific regulatory CD4+ T cell responses by CD137 expression.
40.
Zurück zum Zitat Wang J, Ioan-Facsinay A, van der Voort EIH, Huizinga TWJ, Toes REM. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol. 2007;37:129–38.CrossRefPubMed Wang J, Ioan-Facsinay A, van der Voort EIH, Huizinga TWJ, Toes REM. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol. 2007;37:129–38.CrossRefPubMed
41.
Zurück zum Zitat Bacher P, et al. Antigen-specific expansion of human regulatory T cells as a major tolerance mechanism against mucosal fungi. Mucosal Immunol. 2013;7:916–28.PubMed Bacher P, et al. Antigen-specific expansion of human regulatory T cells as a major tolerance mechanism against mucosal fungi. Mucosal Immunol. 2013;7:916–28.PubMed
42.
Zurück zum Zitat Ryan JF, et al. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets. Proc Natl Acad Sci U S A. 2016;113:E1286–95.CrossRefPubMedPubMedCentral Ryan JF, et al. Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets. Proc Natl Acad Sci U S A. 2016;113:E1286–95.CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Miyao T, et al. Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity. 2012;36:262–75.CrossRefPubMed Miyao T, et al. Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity. 2012;36:262–75.CrossRefPubMed
44.
45.
Zurück zum Zitat Hong X, Wang X. Epigenetics and development of food allergy (FA) in early childhood. Curr Allergy Asthma Rep. 2014;14:460.CrossRefPubMed Hong X, Wang X. Epigenetics and development of food allergy (FA) in early childhood. Curr Allergy Asthma Rep. 2014;14:460.CrossRefPubMed
Metadaten
Titel
Human Immune Monitoring Techniques during Food Allergen Immunotherapy
verfasst von
Blake Rust
Erik Wambre
Publikationsdatum
01.04.2017
Verlag
Springer US
Erschienen in
Current Allergy and Asthma Reports / Ausgabe 4/2017
Print ISSN: 1529-7322
Elektronische ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-017-0689-y

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