Towards a comprehensive view of immunoglobulin class switching

Snapper, Clifford M.; Mond, James J.

doi:10.1016/0167-5699(93)90318-f

Cited by 346 publications

(227 citation statements)

References 36 publications

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“…It has been suggested that the protective effect of antigen-based immunotherapies in type 1 diabetes relies on skewing the Th1 predominant immune response towards a Th2 associated phenotype. As cytokines regulate the generation of different IgG subclasses, distribution of subclass specific antibodies may reflect whether the immune response is Th1 or Th2 skewed [30]. As previously described for type 1 diabetes patients, we found that GADA antibodies were mainly composed of the IgG1 subclass, while the other subclasses are less frequent [31; 32].…”

Section: Discussionsupporting

confidence: 64%

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

Chéramy

Skoglund

Johansson

et al. 2010

Clinical Immunology

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, GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD (65) AbstractWe have previously shown that two injections of 20 μg GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD 65 enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD-alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months.At 3 month a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GADalum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD 65 enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pre-treatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response.

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Section: Discussionsupporting

confidence: 64%

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

Chéramy

Skoglund

Johansson

et al. 2010

Clinical Immunology

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“…This result is consistent with the general pattern of T-cell help induced by LT described by other workers who have studied the cytokines such as INF-γ and IL-5, released by T cells taken from mice following immunization with LT as a mucosal adjuvant (Takahashi et al, 1996). In contrast, LT∆110/112 as well as wild-type LT induced predominant IgG1 responses following IG immunization, which more closely resembled the Th2-type responses induced by CT (Snapper et al, 1993;Marinaro et al, 1995;Douce et al, 1997). Kleanthous et al (1998) showed different IgG1/IgG2a responses following IN, peroral or rectal immunization with recombinant H. pylori urease using wild-type LT as an adjuvant in a Swiss-Webster mouse model.…”

Section: Discussionsupporting

confidence: 91%

The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile enterotoxin varies with immunization routes

Park¹,

Chang²,

Kim³

et al. 2000

Exp Mol Med

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Escherichia coli heat-labile enterotoxin (LT), which causes a characteristic diarrhea in humans and animals, is a strong mucosal immunogen and has powerful mucosal adjuvant activity towards coadministered unrelated antigens. Here we report the different mucosal adjuvanticity of nontoxic LT derivatives, LTS63Y and LT∆110/112, generated by immunizing through two different mucosal routes. Intragastric (

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“…Because serum cytokines were below the level of detection, we analyzed serum Ig isotypes. IFN-␥ promotes IgG2a class switching while IL-4 promotes IgG1 class switching, so concentrations of serum IgG2a and IgG1 reflect Th1 and Th2 responses in vivo (22)(23)(24). The higher IgG2a/IgG1 ratio present in the sera of Tg mice suggests that T-bet overexpression promotes IgG2a class switching and represses IgG1 class switching.…”

Section: Discussionmentioning

confidence: 99%

“…Th1 cells support macrophage activation, delayedtyped hypersensitivity responses, and Ig isotype switching to IgG2a. In contrast, Th2 cells provide efficient help for B cell activation and class switching to IgG1 (22,23). To confirm the Th1-dominant response in T-bet Tg mice, serum IgG levels were measured by ELISA (Table I) …”

Section: Higher Ratio Between Igg2a and Igg1 In T-bet Tg Micementioning

confidence: 99%

Th1 and Type 1 Cytotoxic T Cells Dominate Responses in T-bet Overexpression Transgenic Mice That Develop Contact Dermatitis

Ishizaki¹,

Yamada²,

Yoh

et al. 2007

The Journal of Immunology

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Contact dermatitis in humans and contact hypersensitivity (CHS) in animal models are delayed-type hypersensitivity reactions mediated by hapten-specific T cells. Recently, it has become clear that both CD4+ Th1 and CD8+ type 1 cytotoxic T (Tc1) cells can act as effectors in CHS reactions. T-bet has been demonstrated to play an important role in Th1 and Tc1 cell differentiation, but little is known about its contribution to CHS. In the present study, we used C57BL/6 mice transgenic (Tg) for T-bet to address this issue. These Tg mice, which overexpressed T-bet in their T lymphocytes, developed dermatitis characterized by swollen, flaky, and scaly skin in regions without body hair. Skin histology showed epidermal hyperkeratosis, neutrophil, and lymphocyte infiltration similar to that seen in contact dermatitis. T-bet overexpression in Tg mice led to elevated Th1 Ig (IgG2a) and decreased Th2 Ig (IgG1) production. Intracellular cytokine analyses demonstrated that IFN-γ was increased in both Th1 and Tc1 cells. Furthermore, Tg mice had hypersensitive responses to 2,4-dinitrofluorobenzene, which is used for CHS induction. These results suggest that the level of expression of T-bet might play an important role in the development of contact dermatitis and that these Tg mice should be a useful model for contact dermatitis.

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Towards a comprehensive view of immunoglobulin class switching

Cited by 346 publications

References 36 publications

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile enterotoxin varies with immunization routes

Th1 and Type 1 Cytotoxic T Cells Dominate Responses in T-bet Overexpression Transgenic Mice That Develop Contact Dermatitis

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