A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts

Dullaers, Mélissa; Li, Dapeng; Xue, Yaming; Ni, Ling; Gayet, Ingrid; Morita, Rimpei; Ueno, Hideki; Palucka, Karolina; Banchereau, Jacques; Oh, Sang Kon

doi:10.1016/j.immuni.2008.11.008

Cited by 119 publications

(120 citation statements)

References 48 publications

(85 reference statements)

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“…Therefore, the presence of CD103 + DCs may contribute to T-dependent and T-independent switching to IgA. One soluble factor associated with IgA induc-tion is TGF-b (49,50). We were unable to identify TGF-b production by freshly isolated CD103 + DCs ex vivo (data not shown), whereas surface-bound TGF-b was readily detectable on Tregs after sFliC (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…One issue that will need to be addressed in greater detail is the relationship between Treg and T follicular helper cells in regulating switching to IgA. Although Treg responses in GCs have been shown to aid the specificity of the response and reduce the risk of autoimmunity (54), it is also likely that they can contribute to the magnitude of the switched response to IgA (50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

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Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node

Flores‐Langarica

Marshall

Hitchcock

et al. 2012

The Journal of Immunology

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Mucosal immunity is poorly activated after systemic immunization with protein Ags. Nevertheless, induction of mucosal immunity in such a manner would be an attractive and simple way to overcome the intrinsic difficulties in delivering Ag to such sites. Flagellin from Salmonella enterica serovar Typhimurium (FliC) can impact markedly on host immunity, in part via its recognition by TLR5. In this study, we show that systemic immunization with soluble FliC (sFliC) drives distinct immune responses concurrently in the mesenteric lymph nodes (MLN) and the spleen after i.p. and s.c. immunization. In the MLN, but not the spleen, sFliC drives a TLR5-dependent recruitment of CD103+ dendritic cells (DCs), which correlates with a diminution in CD103+ DC numbers in the lamina propria. In the MLN, CD103+ DCs carry Ag and are the major primers of endogenous and transgenic T cell priming. A key consequence of these interactions with CD103+ DCs in the MLN is an increase in local regulatory T cell differentiation. In parallel, systemic sFliC immunization results in a pronounced switching of FliC-specific B cells to IgA in the MLN but not elsewhere. Loss of TLR5 has more impact on MLN than splenic Ab responses, reflected in an ablation of IgA, but not IgG, serum Ab titers. Therefore, systemic sFliC immunization targets CD103+ DCs and drives distinct mucosal T and B cell responses. This offers a potential “Trojan horse” approach to modulate mucosal immunity by systemically immunizing with sFliC.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node

Flores‐Langarica

Marshall

Hitchcock

et al. 2012

The Journal of Immunology

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“…T FH cells can arise in the absence of factors that mediate Th1, Th2, or Th17 differentiation, but depend on Bcl-6 (2-5). T FH cells express a high level of IL-21, which provides a robust stimulus for proliferation and differentiation of B cells (6,7). IL-21 also plays an indispensible role in the generation of T FH cells, probably by enhancing Bcl-6 expression (3).…”

Section: Cd28 ͉ Follicular B Helper T-cell ͉ Germinal Center ͉ Icos ͉mentioning

confidence: 99%

Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase

Gigoux

Shang

Pak

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

212

258

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The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T FH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in T FH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4 ؉ T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key T FH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of T FH and suggest that CD28 and ICOS play differential roles during a multistep process of T FH differentiation.CD28 ͉ follicular B helper T-cell ͉ germinal center ͉ ICOS ͉ PI3K

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“…For example, the Th1 cytokine interferon-c (IFN-c) regulates immunoglobulin G2a (IgG2a) production, while the Th2 cytokine interleukin-4 (IL-4) is critical to IgG1/IgE class switching 5,6 and transforming growth factor-b (TGF-b) and IL-10 are implicated in the switch to IgA. 7 A recent study also suggested that IL-17 drives autoimmune responses by promoting the spontaneous formation of germinal centers, implicating Th17 cells in the regulation of autoreactive antibodies. 8 Recently, it has been elucidated that a subset of CD4…”

Section: Upon Encountering Their Cognate Antigens On the Surface Of Pmentioning

confidence: 99%

Understanding the development and function of T follicular helper cells

2010

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A fundamental function of T helper (Th) cells is to regulate B-cell proliferation and immunoglobulin class switching, especially in the germinal centers. Th1 and Th2 lineages of CD4 1 T cells have long been considered to play an essential role in helping B cells by promoting the production immunoglobulin G2a (IgG2a) and IgG1/IgE, respectively. Recently, it has become clear that a subset CD4 1 T cells, named T follicular helper (Tfh) cells, is critical to B-cell response induction. In this review, we summarize the latest advances in our understanding of the regulation of Tfh cell differentiation, the relationship of Tfh cells to other CD41 T-cell lineages, and the role of Tfh cells in health and disease.

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A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts

Cited by 119 publications

References 48 publications

Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node

Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node

Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase

Understanding the development and function of T follicular helper cells

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