T helper cells

Noelle, R. J.; Ec, Snow

doi:10.1016/0952-7915(92)90085-s

Cited by 35 publications

(8 citation statements)

References 41 publications

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“…Whereas the role of slg in mediating Ag uptake for subsequent processing and presentation to Th cells is well established (9)(10)(11)(12), the role of slg signal transduction in T cell-dependent Ab responses has remained unclear (59)(60)(61)(62). In particular, it is difficult to reconcile the need for both MHC-restricted B cell Ag presentation and the need for slg signaling with recent studies demonstrating that, in the absence of both events, membrane CD40L together with T cell-derived lymphokines can nevertheless trigger resting B cells to proliferate and produce Ab efficiently (for a review see reference 7).…”

Section: Role Of Slg Signaling In B-t Cell Interactionmentioning

confidence: 99%

“…One of the most important signals is an integral membrane protein, CD40-1igand (CD40L) 1, that is transiently displayed on the surface of activated Th cells and triggers B cell proliferation through a receptor, CD40, constitutively expressed on B cells (5,6). Other molecules secreted by activated Th cells, such as IL-4 and -10, synergize with CD40L in promoting B cell proliferation and in triggering isotype switching and differentiation into plasma cells (for a recent review see reference 7).…”

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confidence: 99%

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Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells.

Cooke

Heath

Shokat

et al. 1994

The Journal of Experimental Medicine

320

261

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SummaryThe specifidty of antibody (Ab) responses depends on focusing helper T (Th) lymphocyte signals to suitable B lymphocytes capable of binding foreign antigens (Ags), and away from nonspecific or self-reactive B cells. To investigate the molecular mechanisms that prevent the activation of self-reactive B lymphocytes, the activation requirements of B cells specific for the Ag hen egg lysozyme (HEL) obtained from immunoglobulin (Ig)-transgenic mice were compared with those of functionally tolerant B cells isolated from Ig-transgenic mice which also express soluble HEL. To eliminate the need for surface (s)Ig-mediated Ag uptake and presentation and allow the effects of slg signaling to be studied in isolation, we assessed the ability of allogeneic T cells from bm12 strain mice to provide in vivo help to C57BL/6 strain-transgenic B cells. Interestingly, nontolerant Ig-transgenic B cells required both allogeneic Th cells and binding of soluble HEL for efl~dent activation and Ab production. By contrast, tolerant self-reactive B cells from Ig/HEL double transgenic mice responded poorly to the same combination of allogeneic T cells and soluble HEL. The tolerant B cells were nevertheless normally responsive to stimulation with interleukin 4 and anti-CD40 Abs in vitro, suggesting that they retained the capacity to respond to mediators of T cell help. However, the tolerant B cells exhibited a proximal block in the slg signaling pathway which prevented activation of receptor-assodated tyrosine kinases in response to the binding of soluble HEL. The functional significance of this slg signaling defect was confirmed by using a more potent membrane-bound form of HEL capable of triggering slg signaling in tolerant B cells, which markedly restored their ability to collaborate with allogeneic Th cells and produce Ab. These findings indicate that Ag-specific B cells require two signals for mounting a T cell-dependent Ab response and identify regulation of slg signaling as a mechanism for controlling self-reactive B cells.

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Section: Role Of Slg Signaling In B-t Cell Interactionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells.

Cooke

Heath

Shokat

et al. 1994

The Journal of Experimental Medicine

320

261

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“…Besides the binding of foreign Ags to BCRs expressed on B cells, accessory signals provided to B cells by Th cells through specific ligand-receptor interactions are indispensable costimulation for B cell proliferation, activation, and subsequent Ab production (2). The most widely studied costimulatory pathway in mammals is the CD154-CD40-mediated signaling pathway (3).…”

mentioning

confidence: 99%

CD154-CD40 Interactions Are Essential for Thymus-Dependent Antibody Production in Zebrafish: Insights into the Origin of Costimulatory Pathway in Helper T Cell-Regulated Adaptive Immunity in Early Vertebrates

Gong

Xiang²,

Shao³

2009

The Journal of Immunology

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The CD154-CD40-mediated costimulatory pathway is critical for T-B cell cooperation in thymus-dependent (TD) immune response in mammals. However, little is known about its existence and occurrence in lower vertebrates. Here, we report on the identification and functional characterization of CD154 and CD40 homologs from the zebrafish (Danio rerio) model. Zebrafish CD154 is a type II membrane-bound protein with a TNF homology domain in its extracellular C-terminal region, whose tertiary structure is a sandwich containing two stacked sheets with “jelly roll” topology, just as the human TNF members do. The zebrafish CD40 is a type I membrane-bound protein with a sequence pattern of four cysteine-rich domains in its extracellular N-terminal region. The consensus TNFR-associated factor (TRAF)2- and TRAF6-binding motifs in mammalian CD40 are found in the cytoplasmic tail of zebrafish CD40, which indicates similar signal transduction mechanisms to higher vertebrates. Zebrafish CD154 and CD40 are widely distributed and can be up-regulated by thymus-dependent Ag. The production of IgM was dramatically decreased by anti-CD154 or soluble CD40, and it was enhanced by soluble CD154 or CD154-encoding plasmid in vivo. Thymus-dependent Ag-induced CD154 expression was inhibited by cyclosporin A, suggesting that CD154 functionally associates with T cells. Double immunofluorescence staining showed that CD40 and membrane IgM colocalized in B cells. CD154-CD40 binding assays showed that CD154 specifically binds to CD40 at homodimeric form. Our results provide the first evidence for the existence of the functional CD154-CD40-mediated costimulatory pathway and helper T cell regulatory mechanism underlying adaptive immunity in a fish species.

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“…However, as has already been mentioned, one of the key roles of IL-5 however is to regulate eosinophil activation, differentiation and survival. Thus, although IL-5 also helps in the activation of B cells (Noelle et al 1992), its major role is to recruit and activate eosinophils which act in concert with mast cells and IgE producing B cells in the immune response against parasites and in pathophysiology of allergic disease. The relative importance of these pathways is likely to vary according to the specific 'allergic' disease state.…”

Section: Il-5 the Th2 Cytokine Profile And Allergic In-flammationmentioning

confidence: 99%

IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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and a soluble isoform (αIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of αIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased

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T helper cells

Cited by 35 publications

References 41 publications

Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells.

Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells.

CD154-CD40 Interactions Are Essential for Thymus-Dependent Antibody Production in Zebrafish: Insights into the Origin of Costimulatory Pathway in Helper T Cell-Regulated Adaptive Immunity in Early Vertebrates

IL-5 and IL-5 receptor in asthma

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