CD28 co‐signaling in the adaptive immune response

Riha, Pavel; Rudd, Christopher E.

doi:10.4161/self.1.3.12968

Cited by 77 publications

(67 citation statements)

References 128 publications

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“…2F). Hence, ifenprodil impairs T-cell activation by attenuating important TCR-induced signaling events, including Ca 2ϩ flux and the activation of PLC-␥1, Erk1/2, Akt, and NFATc1, and this inhibition can be compensated for, at least partially, by CD28 signaling (29)(30)(31)(32).…”

Section: Cd4mentioning

confidence: 99%

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of K_v1.3 and K_Ca3.1 Channels in T Cells

Kahlfuß

Simma

Mankiewicz

et al. 2014

Molecular and Cellular Biology

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Section: Cd4mentioning

confidence: 99%

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of K_v1.3 and K_Ca3.1 Channels in T Cells

Kahlfuß

Simma

Mankiewicz

et al. 2014

Molecular and Cellular Biology

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“…CD28 increases traction forces through intracellular signaling as opposed to providing additional traction through this costimulatory receptor. To delineate these signaling pathways, we examined phosphoinositide 3-kinase (PI3K), which binds to the cytosolic domain of CD28, leading to conversion of PIP 2 to PIP 3 , activation of PKB (Akt) and phosphoinositide-dependent kinase 1 (PDK1), and subsequent signaling (16,23,24) (Fig. 2 C and E).…”

Section: Human Primary T Cells Generate Traction Forces On Surfaces Ementioning

confidence: 99%

“…Activating antibodies to CD3 (epsilon chain) and CD28, which provide antigenindependent signaling of the TCR complex and costimulation, respectively (14)(15)(16), were attached to polymer and hydrogel supports and presented to primary T cells. Multiple cellular functions, including Interleukin-2 (IL-2) secretion and proliferation, responded to the rigidity of the substrate, echoing the phenomenon of mechanosensing observed in other types of cells interacting with ECM.…”

mentioning

confidence: 99%

CD28 and CD3 have complementary roles in T-cell traction forces

Bashour¹,

Gondarenko

Chen³

et al. 2014

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

215

251

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Mechanical forces have key roles in regulating activation of T cells and coordination of the adaptive immune response. A recent example is the ability of T cells to sense the rigidity of an underlying substrate through the T-cell receptor (TCR) coreceptor CD3 and CD28, a costimulation signal essential for cell activation. In this report, we show that these two receptor systems provide complementary functions in regulating the cellular forces needed to test the mechanical properties of the extracellular environment. Traction force microscopy was carried out on primary human cells interacting with micrometer-scale elastomer pillar arrays presenting activation antibodies to CD3 and/or CD28. T cells generated traction forces of 100 pN on arrays with both antibodies. By providing one antibody or the other in solution instead of on the pillars, we show that force generation is associated with CD3 and the TCR complex. Engagement of CD28 increases traction forces associated with CD3 through the signaling pathway involving PI3K, rather than providing additional coupling between the cell and surface. Force generation is concentrated to the cell periphery and associated with molecular complexes containing phosphorylated Pyk2, suggesting that T cells use processes that share features with integrin signaling in force generation. Finally, the ability of T cells to apply forces through the TCR itself, rather than the CD3 coreceptor, was tested. Mouse cells expressing the 5C.C7 TCR exerted traction forces on pillars presenting peptide-loaded MHCs that were similar to those with α-CD3, suggesting that forces are applied to antigen-presenting cells during activation.T -cell activation is a key regulatory point of the adaptive immune response. It is initiated by recognition of peptideloaded MHCs (pMHCs) on antigen-presenting cells (APCs) by T-cell receptors (TCRs). Engagement of additional receptors on the T-cell surface leads to formation of a specialized interface termed the immune synapse (IS), which focuses communication between these cells. The IS has emerged as a compelling model of juxtacrine signaling, providing key insights into how the dynamics of such interfaces influence cell-cell communication. Mechanical forces originating from a range of sources, including cytoskeletal dynamics, also play important roles in T-cell activation. The initial spreading of T cells following contact with an activating surface is dependent on a burst of actin polymerization (1, 2). Subsequent retrograde flow of actin and contraction of actomyosin structures drive microscale reorganization of signaling complexes within this interface, resulting in formation of concentric central, peripheral, and distal supramolecular activation cluster (cSMAC, pSMAC, and dSMAC) structures that comprise the archetypal IS (3-8). The TCR complex itself may be triggered by external forces (9, 10), whereas TCR ligation may induce actin polymerization and generation of protrusive forces (11).More recently, mechanosensing by T cells was demonstrated in the context ...

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“…Costimulatory receptors on T cell surfaces can induce positive intracellular signaling pathways, while coinhibitory signals can either induce negative signaling pathways or disrupt signaling mechanisms after binding a ligand or a counterreceptor on APCs or other cell types (1). Coinhibitory molecules, including PD-1, Tim-3, BTLA, CTLA-4, Lag-3, and CD160, play critical roles in the negative regulation of T cell responses in lymphoid organs and peripheral nonlymphoid tissues to control immune responses and inflammation (1)(2)(3)(4). With few exceptions, coinhibitory receptors and/or ligands are induced after T cell activation and serve as a negative feedback mechanism that controls T cell responses.…”

Section: Introductionmentioning

confidence: 99%

Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity

Flies¹,

Han²,

Higuchi³

et al. 2014

J. Clin. Invest.

236

286

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CD28 co‐signaling in the adaptive immune response

Cited by 77 publications

References 128 publications

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of K_v1.3 and K_Ca3.1 Channels in T Cells

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of K_v1.3 and K_Ca3.1 Channels in T Cells

CD28 and CD3 have complementary roles in T-cell traction forces

Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity

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CD28 co‐signaling in the adaptive immune response

Cited by 77 publications

References 128 publications

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of Kv1.3 and KCa3.1 Channels in T Cells

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of Kv1.3 and KCa3.1 Channels in T Cells

CD28 and CD3 have complementary roles in T-cell traction forces

Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity

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Product

Resources

About

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of K_v1.3 and K_Ca3.1 Channels in T Cells

Immunosuppression by N-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of K_v1.3 and K_Ca3.1 Channels in T Cells