Circulating CLA<sup>+</sup> lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal‐related T‐cell receptor variable segments

Torres, Mauricio; González, Francisco García; Corzo, José Luís; Girón, María D.; Carvajal, M.J.; García, Verónica; Pinedo, A. Bodas; Martínez-Valverde, Antonio; Blanca, Miguel; Santamaría, L.F.

doi:10.1046/j.1365-2222.1998.00397.x

Cited by 31 publications

(29 citation statements)

References 33 publications

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“…In addition, Torres observed a significantly increased percentage of CLA þ Vb5.1 þ T cells in children with AD compared with normal controls (Torres et al, 1998). Most other studies that evaluated the Vb repertoire in AD have, however, not shown an increase in Vb5.1 in the skin (Neuber et al, 1996;Yudate et al, 1996;Bunikowski et al, 2000), nor blood of AD patients (Strickland et al, 1999;Bunikowski et al, 2000;Davison et al, 2000) compared to normal controls, and Neuber et al (1996) actually found a significantly decreased percentage of Vb5.1 þ T cells in the skin of AD.…”

Section: Discussionmentioning

confidence: 93%

“…For example, the skin of patients with AD is often colonized by enterotoxin-producing strains of Staphylococcus aureus, and these superantigenic toxins are capable of skewing the Vb subfamily repertoire in skin-homing T cells as well as increasing expression of the skin-homing receptor, CLA (Leung et al, 1995;Neuber et al, 1996;Torres et al, 1998;Dworzak et al, 1999;Strickland et al, 1999;Bunikowski et al, 2000;Davison et al, 2000;Zollner et al, 2000;Breuer et al, 2002). Even with healthy individuals, molecular studies have shown differences in Vb family expression in skin samples compared with the blood, suggesting an effect of the microenvironment of the T cell repertoire (Dunn et al, 1993;Ahangari et al, 1996;Menssen et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Vonderheid

Boselli

Conroy

et al. 2005

Journal of Investigative Dermatology

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Antibodies directed against the beta chain of the T cell receptor (anti-Vbeta antibodies) are useful to identify the Vbeta repertoire of T cells in various diseases and to quantify numbers of Vbeta-bearing T cells. The goals of this study were to identify Vbeta+ cases of leukemic phase cutaneous T cell lymphoma (CTCL) and to compare the percentage of positive calls with other measures of blood tumor burden, i.e., lymphocyte subsets with a CD4+CD7- and CD4+CD26- phenotype and Sezary cell counts. Thirty-three of 49 (67%) cases of leukemic CTCL reacted with an anti-Vbeta antibody. When combined with reports from the literature, the frequency of Vbeta5 (probably Vbeta5.1) usage was relatively high when compared with Vbeta2 that is also frequently expressed by normal CD4+ T cells. The percentage of Vbeta+ cells correlated to the percentage of CD4+CD7- and CD4+CD26- cells for cases in which the neoplastic cells were deficient in expression of CD7 and CD26, respectively, but not the Sezary cell count. We hypothesize that the increased Vbeta5.1 usage in CTCL may be the result of depletion of Vbeta2 and other Vbeta-bearing T cells by staphylococcal superantigens prior to neoplastic transformation, resulting in a relative increase in the frequency of Vbeta5.1 usage in CTCL.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Vonderheid

Boselli

Conroy

et al. 2005

Journal of Investigative Dermatology

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“…44, 89 In addition, increased S. aureus colonization, as evidenced by increased T-cell receptor (TCR) Vβ expression on CLA + T-cells, 90 underdeveloped IL-22, reduced IL-17 and suppressed IFN-γ, all considered protective cytokines against pathogens, 91–98 might orchestrate the immune milieu, rendering AD children more susceptible to skin infections. 99, 100 …”

Section: Discussionmentioning

confidence: 99%

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

Czarnowicki

Esaki

Gonzalez

et al. 2015

Journal of Allergy and Clinical Immunology

192

171

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Background Identifying differences and similarities between CLA+ polarized T-cell subsets in pediatric vs. adult atopic dermatitis (AD) is critical for directing new treatments towards children. Objective To compare activation markers and frequencies of skin-homing (CLA+) vs. systemic (CLA−) “polar” CD4 and CD8 T-cell subsets in early pediatric AD, adult AD and controls. Methods Flow cytometry was used to measure CD69/ICOS/HLA-DR frequency in memory subsets as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining Th1/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, and Th22/Tc22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children <5 years and 42 adults with well-characterized moderate to severe AD, as well as age-matched controls (17 children and 25 adults). Results Selective ICOS activation (P<0.001) was seen in children. CLA+ Th2 T-cells were markedly expanded in both AD children and adults compared to controls, but decreases in CLA+ Th1 T-cells were greater in AD children (17% vs. 7.4%, P=0.007). Unlike in adults, no imbalances were detected in pediatric AD CLA− T-cells, nor were there altered frequencies of Th22 T-cells within CLA+ or CLA− compartments. Adults with AD had increased frequency of IL-22-producing CD4 and CD8 T-cells within the skin-homing population (9.5% vs. 4.5%; 8.6% vs. 2.4%, respectively; P<0.001) as well as increased HLA-DR activation (P<0.01). Conclusions These data suggest that Th2 activation within skin-homing T-cells may drive AD in children and that reduced counter-regulation by Th1 T-cells may contribute to excess Th2 activation. Th22 “spreading” of AD is not seen in young children and may be influenced by immune development, disease chronicity or recurrent skin infections. Clinical Implications Therapeutic approaches to treat AD in children may be best directed to correction of Th2/Th1 imbalance, while adults might also benefit from IL-22 targeted therapies.

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“…Most T cells infiltrating inflammed skin are CLA-positive, whereas CLA is not expressed on the T cells present in other inflammatory tissues. Previous studies indicated that AD patients had a higher percentage of T cells bearing SsAg-reactive TCRVβ in the peripheral blood CLA + T cells than healthy subjects [106,107]. Leung et al [108] showed that IL-12 is the most important cytokine in the induction of CLA expression on T cells.…”

Section: Expansion Of Skin-homing Cutaneous Lymphocyteassociated Antimentioning

confidence: 99%

Role of Bacterial Pathogens in Atopic Dermatitis

Lin

Wang

Chiang

2007

Clinic Rev Allerg Immunol

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The skin of atopic dermatitis (AD) patients exhibits a striking susceptibility to colonization and infection with Staphylococcus aureus. This review summarizes our understanding about the role of S. aureus in AD. Indeed, S. aureus colonization is both a cause and a consequence of allergic skin inflammation. The mechanisms that allergic skin inflammation of AD promotes the increase of S. aureus colonization include skin barrier dysfunction, increased synthesis of the extracellular matrix adhesins for S. aureus, and defective innate immune responses due to decreased production of endogenous antimicrobial peptides. On the other hand, the exotoxins secreted by S. aureus are superantigens. Staphylococcal superantigens (SsAgs) may penetrate the skin barrier and contribute to the persistence and exacerbation of allergic skin inflammation in AD through the stimulation of massive T cells, the role of allergens, direct stimulation of antigen-presenting cells and keratinocytes, the expansion of skin-homing cutaneous lymphocyte-associated antigen-positive T cells, and the augmentation of allergen-induced skin inflammation. SsAgs also induce corticosteroid resistance. In therapeutic interventions, anti-inflammatory therapy alone is very effective in reducing S. aureus colonization on the skin, but antibiotic treatment alone is unable to improve the allergic skin inflammation of AD. Therefore, we recommend the combination therapy of anti-inflammatory drugs and antibiotics in the AD patients with secondary bacterial infection, exacerbated AD, or poorly controlled AD. However, when AD is well controlled by anti-inflammatory drugs alone, we do not recommend the antibiotic therapy.

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Circulating CLA⁺ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal‐related T‐cell receptor variable segments

Cited by 31 publications

References 33 publications

Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

Role of Bacterial Pathogens in Atopic Dermatitis

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Circulating CLA+ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal‐related T‐cell receptor variable segments

Cited by 31 publications

References 33 publications

Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Evidence for Restricted Vβ Usage in the Leukemic Phase of Cutaneous T Cell Lymphoma

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

Role of Bacterial Pathogens in Atopic Dermatitis

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Circulating CLA⁺ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal‐related T‐cell receptor variable segments