Functional regulatory T cells and allergen immunotherapy

被引:40
作者
Rolland, Jennifer M. [2 ]
Gardner, Leanne M. [1 ,2 ]
O'Hehir, Robyn E. [1 ,2 ]
机构
[1] Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic 3004, Australia
[2] Monash Univ, Dept Immunol, Melbourne, Vic 3004, Australia
基金
英国医学研究理事会;
关键词
allergen immunotherapy; allergy; regulatory T cells; GRASS-POLLEN IMMUNOTHERAPY; COWS MILK ALLERGY; HOUSE-DUST MITE; TGF-BETA; FOXP3; EXPRESSION; DENDRITIC CELLS; INDUCTION; TOLERANCE; CHILDREN; STIMULATION;
D O I
10.1097/ACI.0b013e32833ff2b2
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Purpose of review Burgeoning literature ascribing roles for regulatory T cells (Treg) in controlling clinical allergy frequently relies on phenotypic markers rather than functional suppression assays. This review examines evidence for functional Treg in controlling immune responses to allergen with particular focus on allergen-specific immunotherapy. Recent findings Over the last year, use of recently identified Treg markers has facilitated more precise delineation and isolation of Treg subtypes. Advanced flow cytometry allows better discrimination and tracking of effector T cells (Teff) and Treg in co-culture assays for Treg function. These approaches enable critical appraisal of the evidence for Treg mediation of the observed changes in immune reactivity to allergen accompanying immunotherapy. Recent studies suggest that different mechanisms of immune regulation may occur at different times of immunotherapy, with Treg playing a more important role early in treatment. Additionally, advanced imaging techniques reveal increased Treg numbers in allergen-exposed mucosal tissue after therapy consistent with an enhanced local functional role. Summary These findings support a mechanistic role for Treg early in allergen immunotherapy. Research is required to clarify the precise Treg subsets involved, their specificity and how their activity can be enhanced during immunotherapy by appropriate allergen form, optimal site of administration and use of adjuvants and adjunct therapies.
引用
收藏
页码:559 / 566
页数:8
相关论文
共 81 条
[1]   Chemokine responsiveness of CD4+CD25+regulatory and CD4+CD25-T cells from atopic and nonatopic donors [J].
Ahern, D. ;
Lloyd, C. M. ;
Robinson, D. S. .
ALLERGY, 2009, 64 (08) :1121-1129
[2]   Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells [J].
Akdis, M ;
Verhagen, J ;
Taylor, A ;
Karamloo, F ;
Karagiannidis, C ;
Crameri, R ;
Thunberg, S ;
Deniz, G ;
Valenta, R ;
Fiebig, H ;
Kegel, C ;
Disch, R ;
Schmidt-Weber, CB ;
Blaser, K ;
Akdis, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (11) :1567-1575
[3]   Mechanisms of allergen-specific immunotherapy [J].
Akdis, Muebeccel ;
Akdis, Cezmi A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (04) :780-789
[4]   Therapeutic manipulation of immune tolerance in allergic disease [J].
Akdis, Muebeccel ;
Akdis, Cezmi A. .
NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (08) :645-660
[5]   Dendritic cells as potential targets for mucosal immunotherapy [J].
Allam, Jean P. ;
Bieber, Thomas ;
Novak, Natalija .
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 9 (06) :554-557
[6]   Seasonal changes in suppressive capacity of CD4+ CD25+ T cells from patients with hayfever are allergen-specific and may result in part from expansion of effector T cells among the CD25+ population [J].
Anderson, A. E. ;
Mackerness, K. J. ;
Aizen, M. ;
Carr, V. A. ;
Nguyen, D. ;
Du Pre, F. ;
Durham, S. R. ;
Robinson, D. S. .
CLINICAL AND EXPERIMENTAL ALLERGY, 2009, 39 (11) :1693-1699
[7]   CD4+CD25high regulatory cells in human peripheral blood [J].
Baecher-Allan, C ;
Brown, JA ;
Freeman, GJ ;
Hafler, DA .
JOURNAL OF IMMUNOLOGY, 2001, 167 (03) :1245-1253
[8]   The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 [J].
Bennett, CL ;
Christie, J ;
Ramsdell, F ;
Brunkow, ME ;
Ferguson, PJ ;
Whitesell, L ;
Kelly, TE ;
Saulsbury, FT ;
Chance, PF ;
Ochs, HD .
NATURE GENETICS, 2001, 27 (01) :20-21
[9]   Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation [J].
Bohle, Barbara ;
Kinaciyan, Tamar ;
Gerstmayr, Marianne ;
Radakovics, Astrid ;
Jahn-Schmid, Beatrice ;
Ebner, Christof .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 120 (03) :707-713
[10]   Expression of ectonucleotidase CD39 by Foxp3+ Treg cells:: hydrolysis of extracellular ATP and immune suppression [J].
Borsellino, Giovanna ;
Kleinewietfeld, Markus ;
Di Mitri, Diletta ;
Sternjak, Alexander ;
Diamantini, Adamo ;
Giometto, Raffaella ;
Hoepner, Sabine ;
Centonze, Diego ;
Bernardi, Giorgio ;
Dell'Acqua, Maria Luisa ;
Rossini, Paolo Maria ;
Battistini, Luca ;
Rotzschke, Olaf ;
Falk, Kirsten .
BLOOD, 2007, 110 (04) :1225-1232