The Influence of Costimulation and Regulatory Cd4<sup>+</sup> T Cells on Intestinal Iga Immune Responses

Gärdby, Eva; Kagrdic, Dubrav; Kjerrulf, Martin; Bromander, Annakari; Vajdy, Michael; Hörnquist, Elisabeth Hultgren; Lycke, Nils

doi:10.1155/1998/75718

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…It has been proposed that in mice a proportion of the specific SIgA against commensal bacteria are induced in a T cell-independent pathway, independent of the development of follicular lymphoid structures 44, 45 . Subsequent studies in mice revealed that commensal bacteria persist in Peyer's patch DCs, contributing to induction of local specific immune responses that limit dissemination no farther than the MLNs, ultimately preventing systemic spread 46 .…”

Section: Role Of Siga In Homeostasis Of the Intestinal Microbiotamentioning

confidence: 99%

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut

2011

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Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence the composition of the intestinal microbiota by Fab-dependent and -independent mechanisms, promote the retro-transport of antigens across the intestinal epithelium to dendritic cell (DC) subsets in gut-associated lymphoid tissue, and, finally, to down-regulate pro-inflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships to immunity and intestinal homeostasis.

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Section: Role Of Siga In Homeostasis Of the Intestinal Microbiotamentioning

confidence: 99%

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut

2011

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“…Gardby et al have recently demonstrated that CD4 knockout mice, IL-4 knockout mice and mice made transgenic for CTLA-4 Ig, while demonstrating impairment of speci®c IgG responses, show normal mucosal IgA B-cell differentiation and IgA production [60,61]. Also, the loss of CD4 T-helper cells from mucosal tissues of the small intestine does not affect the relative frequency of mIgA B cells in Peyer's Patch [62], which suggests that CD4 T cells do not in¯uence isotype switch to IgA.…”

Section: Do Cd4 T Cells Play An Important Role In Iga Production?mentioning

confidence: 99%

Could the airway epithelium play an important role in mucosal immunoglobulin A production?

Salvi

Holgate

1999

Clin Experimental Allergy

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Immunoglobulin (Ig) A is the major immunoglobulin of the healthy respiratory tract and is thought to be the most important immunoglobulin for lung defence. The basis for the preferential generation of IgA-secreting cells in the airway mucosa remains unclear. Given the half-life of 5 days for the majority of IgA plasma cells, many IgA plasma cells must develop daily from B cells to guarantee a continuous supply of IgA antibodies in the airway mucosa. For this, the surrounding cells must provide a constant supply of cytokines necessary for B-cell isotype switch, growth and differentiation into IgA-secreting plasma cells. Studies with CD4+ T-cell knockout mice, T-cell receptor knockout mice and mice made transgenic for CTLA4-Ig demonstrate normal mucosal IgA isotype switch, differentiation and IgA production, thereby suggesting that T cells are not critical for mucosal IgA production, and that other cell sources may be more important. Also, the bronchus-associated lymphoid tissue (BALT), which is believed to be the major site where IgA isotype switch and differentiation of B cells into plasma cells occur with the help of cytokines released by T cells, is not a constitutive feature of the normal human lung. This indicates that other parts of the respiratory tract must carry out the BALT function. We have recently demonstrated that healthy human airway epithelial cells constitutively produce IL-5, a major cytokine implicated in the growth and differentiation of post-switch mIgA+ B cells to IgA-producing plasma cells. Several studies have recently reported that the human airway epithelium also constitutively produces IL-2, TGFbeta, IL-6 and IL-10, factors which are essential for B-cell clonal proliferation, IgA isotype switch and differentiation into IgA-producing plasma cells. The close proximity of B cells to the airway epithelium probably ensures a constant supply of growth and differentiation factors necessary for mucosal IgA production. In addition, the epithelial cells produce a glycoprotein, called the secretory component, which not only confers increased stability to S-IgA, but is also quantitatively the most important receptor of the mucosal immune system, since it is responsible for the external transport of locally produced polymeric IgA and IgM. Recent studies also suggest a possible role for epithelial cells in antigen presentation. Dendritic cells situated within the airway epithelium could directly present antigens to B cells and direct their isotype switch towards IgA1 and IgA2 with the help of cytokines produced by epithelial cells. Airway epithelial cells could therefore play a major role in the production of mucosal IgA antibodies which are essential for airway mucosal defence.

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“…IL‐5 is also an important cytokine for inducing IgA production 16–18 . To understand whether the TLR4 mutation causes increased numbers of IL‐5‐producing cells in CD4 + T‐cell population of iLP, C3H/He and C3H/HeJ mice were orally immunized with CT, and IL‐5‐producing cells were enumerated by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…IL-5 is also an important cytokine for inducing IgA production. [16][17][18] To understand whether the TLR4 mutation causes increased numbers of IL-5-producing cells in CD4 + T-cell population of iLP, C3H/He and C3H/HeJ mice were orally immunized with CT, and IL-5-producing cells were enumerated by flow cytometry. The percentage of IL-5producing cells significantly increased in the C3H/HeJ mice compared with that of C3H/He mice (Fig.…”

Section: Cytokine Production In Ilpmentioning

confidence: 99%

Mechanism of up‐regulation of immunoglobulin A production in the intestine of mice unresponsive to lipopolysaccharide

et al. 2005

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Summary The mechanisms by which immunoglobulin A (IgA) production up‐regulates in the intestine of Toll‐like receptor‐4 (TLR4)‐mutated mice were investigated. When TLR4‐mutated, C3H/HeJ and BALB/lpsd mice received oral administration of cholera toxin (CT), not only CT‐specific IgA levels in the intestinal lavage but also the number of IgA‐producing cells in intestinal lamina propria (iLP) significantly increased compared with those of the wild‐type C3H/He and BALB/c mice. Interleukin (IL)‐5‐producing cells and CD86+ cells in iLP also significantly increased in C3H/HeJ mice. The expression of major histocompatibility complex class II and CD86 on cells present in Peyer's patches (PPs) of C3H/HeJ mice was higher than those of C3H/He mice. In non‐immunized C3H/HeJ mice, the expression of transforming growth factor‐β (TGF‐β) mRNA and the percentages of IL‐10‐producing cells in PPs but not in spleen increased when compared with those in C3H/He mice. The suppressor of cytokine signalling‐1 (SOCS‐1) was expressed in PPs of C3H/He mice but not C3H/HeJ mice. These results indicate that high IgA levels in the intestine of TLR4‐mutated mice are due to up‐regulation of TGF‐β and IL‐10 and the lack of regulation by SOCS‐1.

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The Influence of Costimulation and Regulatory Cd4⁺ T Cells on Intestinal Iga Immune Responses

Cited by 9 publications

References 28 publications

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut

Could the airway epithelium play an important role in mucosal immunoglobulin A production?

Mechanism of up‐regulation of immunoglobulin A production in the intestine of mice unresponsive to lipopolysaccharide

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The Influence of Costimulation and Regulatory Cd4+ T Cells on Intestinal Iga Immune Responses

Cited by 9 publications

References 28 publications

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut

Could the airway epithelium play an important role in mucosal immunoglobulin A production?

Mechanism of up‐regulation of immunoglobulin A production in the intestine of mice unresponsive to lipopolysaccharide

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The Influence of Costimulation and Regulatory Cd4⁺ T Cells on Intestinal Iga Immune Responses