Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation

Arestides, Ruth S. S.; He, Hongzhen; Westlake, Robert M.; Chen, Andrew I.; Sharpe, Arlene H.; Perkins, David L.; Finn, Patricia W.

doi:10.1002/1521-4141(2002010)32:10<2874::aid-immu2874>3.0.co;2-4

Cited by 97 publications

(68 citation statements)

References 38 publications

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“…In conclusion, CD28 signals recruit PKC isotypes and VAV/SLP-76 complex to active canonical, nocanonical NF-κB pathways, and MAP/JNK kinase pathways that regulate cytokine production. In contrast, blockade of OX40 signals reduces IFN-γ, IL-2, IL-4 and IL-13 secretion and inhibits T cell proliferation, implying OX40 signals may mediate both Th1 and Th2 subtype differentiation (54). It has been suggested a number of years ago that B cell costimulation via the OX40/ OX40L pathway was required for T cell expansion, survival, and Th2 development.…”

Section: Intracellular Signals Of Costimulation In T Cell Responsementioning

confidence: 99%

Intracellular Signals of T Cell Costimulation

et al. 2008

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Section: Intracellular Signals Of Costimulation In T Cell Responsementioning

confidence: 99%

Intracellular Signals of T Cell Costimulation

et al. 2008

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“…Mice deficient in OX40 or OX40L have diminished antigen specific clonal expansion and memory T cell populations [8][9][10][11][12][13]. Blocking OX40/ OX40L interactions in vivo decreases the severity of inflammatory diseases such as GVH disease [14], EAE [15], and asthma [10,16]. In contrast, agonist OX40 antibody increases clonal expansion [9], promotes robust memory T cell populations [17,18], and enhances anti-tumor immunity [19][20][21].…”

Section: Introductionmentioning

confidence: 92%

OX40 (CD134) engagement drives differentiationof CD4⁺ T cells to effector cells

2006

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Naive, CD4+ T cells proliferate extensively but fail to differentiate when they are transferred into unirradiated recipients that express alloantigen or transgenic antigen on all MHC class II+ cells. Addition of an agonist antibody to OX40 (CD134), a costimulatory TNF receptor family member expressed on activated CD4+ T cells, enables the proliferating T cells to accumulate as differentiated effector cells and kill the host animals. The donor T cells from anti‐OX40‐treated animals express high levels of IL‐2Rα (CD25) and acquire the ability to secrete IFN‐γ when stimulated with IL‐12 and IL‐18. OX40 promotes differentiation by 48 h in T cell priming, before changes in Bcl‐2 expression or cell recovery become apparent. We found that a Bcl‐2 transgene or deficiency in Fas or TNFR1 failed to influence accumulation of differentiated donor cells, and found larger changes in expression of cytokine and cytokine receptor genes than in survival genes. Accumulation of differentiated CD4+ effector T cells is initiated directly through OX40, but some OX40‐deficient donor cells can gain effector function as bystanders to OX40+/+ cells. Taken together, these data suggest that CD4+ T cell differentiation to effector function is an important effect of OX40 engagement under conditions of ubiquitous antigen presentation.

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“…Mice were sensitized and challenged with allergen ovalbumin (OVA) as previously described (4,(10)(11)(12)(13)(14)(15). Briefly, mice were sensitized by intraperitoneal injection with 10 g chicken OVA and 1 mg Al(OH) 3 (alum) on Days 0 and 7.…”

Section: Protocol For Allergen Sensitization and Challengementioning

confidence: 99%

“…Total serum IgE levels were determined by ELISA as previously described (12)(13)(14). Total serum IgE concentrations were calculated using a standard curve generated with commercial IgE standard (BD Pharmingen, San Diego, CA).…”

Section: Serum Igementioning

confidence: 99%

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The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

Wang

Campo²,

Ting³

et al. 2006

Am J Respir Cell Mol Biol

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T-cell activation plays an essential role in the generation of the pulmonary inflammation that is manifest in allergic asthma. Optimal T-cell activation requires not only presentation of antigen with the major histocompatibility complex, but also concurrent signaling through costimulatory molecules. The costimulatory molecule SLAM (Signaling Lymphocytic Activation Molecule, CD150) is a glycoprotein expressed on activated lymphocytes and antigenpresenting cells. Disruption of the SLAM gene demonstrated that SLAM-induced signal transduction pathways regulate cytokine production by T helper (Th)2 cells and macrophages. Here we tested the postulate that the costimulatory molecule SLAM may be critical for allergic inflammation in a murine model. SLAM-deficient mice did not manifest allergen-induced bronchoalveolar lavage eosinophilia, increased serum IgE, or heightened airway responses compared with wild-type mice. Allergen-induced Th2 cytokines and Th1 cytokines were decreased in SLAM-deficient mice. These data support the concept that SLAM plays a crucial role in allergic responses.

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Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation

Cited by 97 publications

References 38 publications

Intracellular Signals of T Cell Costimulation

Intracellular Signals of T Cell Costimulation

OX40 (CD134) engagement drives differentiationof CD4⁺ T cells to effector cells

The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

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Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation

Cited by 97 publications

References 38 publications

Intracellular Signals of T Cell Costimulation

Intracellular Signals of T Cell Costimulation

OX40 (CD134) engagement drives differentiationof CD4+ T cells to effector cells

The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses

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Product

Resources

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OX40 (CD134) engagement drives differentiationof CD4⁺ T cells to effector cells