A two-step, two-signal model for the primary activation of precursor helper T cells

Bretscher, Peter A.

doi:10.1073/pnas.96.1.185

Cited by 333 publications

(261 citation statements)

References 59 publications

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“…T cell activation leads to proliferation, which is regulated by two distinct signals (Bretscher 1999). Signal one is generally derived from the TCR, thereby ensuring Ag-specific responses.…”

Section: Introductionmentioning

confidence: 99%

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Ando

Yasuoka

Mishima

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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T cell activation is regulated by two distinct signals, signal one and two. Concanavalin A (ConA) is an antigen-independent mitogen and functions as signal one inducer, leading T cells to polyclonal proliferation. CD28 is known to be one of major costimulatory receptors and to provide signal two in the ConA-induced T cell proliferation. Here, we have studied the implication of other costimulatory pathways in the ConA-mediated T cell proliferation by using soluble recombinant proteins consisting of an extracellular domain of costimulatory receptors and Fc portion of human IgG. We found that T cell proliferation induced by ConA, but not PMA plus ionomycin or anti-CD3 mAb, is significantly inhibited by HVEM-Ig, even in the presence of CD28 signaling. Moreover, the high concentration of HVEM-Ig molecules almost completely suppressed ConA-mediated T cell proliferation. These results suggest that HVEM might play more important roles than CD28 in ConA-mediated T cell proliferation.

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Section: Introductionmentioning

confidence: 99%

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Ando

Yasuoka

Mishima

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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“…The first signal, an Ag, ensures the specificity of activation and is transduced via the T cell Ag receptor. Second signals for T cells are costimulators and cytokines that promote clonal expansion of the specific T cells and their differentiation into effector and memory cells (1). In addition, the immune system provides for control mechanisms, which maintain homeostasis after active immune responses to foreign Ags, and prevent or abort responses to self-Ags.…”

mentioning

confidence: 99%

Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

Prager

Staffler

Majdic

et al. 2001

The Journal of Immunology

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CD31 is a member of the Ig superfamily expressed on various cell types of the vasculature, including a certain subpopulation of T lymphocytes. Previous reports suggest that interaction of CD31 with its heterophilic ligand on T cells (T cell CD31 ligand) plays a regulatory role in T lymphocyte activation. Here we demonstrate that a soluble rCD31-receptorglobulin (CD31Rg) specifically down-regulated the proliferation of human peripheral blood CD31− T lymphocytes stimulated via CD3 and CD28 mAbs. Notably, engagement of the T cell CD31 ligand by CD31Rg during primary stimulation also induced a prolonged unresponsive state in T cells. Retroviral transduction of CD31 into CD31− Th clones resulted in a significant inhibition of their proliferative capacity. When cocultured with purified CD31− T lymphocytes, irradiated CD31-transduced Th clones counterregulated the CD3/CD28-mediated activation of these cells. Furthermore, primary stimulation in the presence of CD31-transduced Th clones induced a comparable state of hyporesponsiveness in the T cell responders as the soluble CD31Rg. Thus, by counterregulating the activation of cognate T lymphocytes, CD31-expressing T cells might contribute to the establishment and maintenance of peripheral tolerance.

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“…One means of regulation is the additional necessity for B7-1 (CD80)/ B7-2 (CD86) costimulatory signals, along with T-cell receptor stimulation, in T-cell activation (1). Reciprocally, soluble recombinant formulations of the natural high-affinity B7 ligandcytotoxic T-lymphocyte antigen 4 fused with human Ig (CTLA4-Ig), which blocks B7 costimulation-are efficacious in neutralizing aberrant T-cell activation in autoimmune disorders such as rheumatoid arthritis and juvenile idiopathic arthritis (2).…”

mentioning

confidence: 99%

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Luo¹,

Jiang²,

Chaturvedi³

et al. 2014

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

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The costimulatory B7-1 (CD80)/B7-2 (CD86) molecules, along with T-cell receptor stimulation, together facilitate T-cell activation. This explains why in vivo B7 costimulation neutralization efficiently silences a variety of human autoimmune disorders. Paradoxically, however, B7 blockade also potently moderates accumulation of immune-suppressive regulatory T cells (Tregs) essential for protection against multiorgan systemic autoimmunity. Here we show that B7 deprivation in mice overrides the necessity for Tregs in averting systemic autoimmunity and inflammation in extraintestinal tissues, whereas peripherally induced Tregs retained in the absence of B7 selectively mitigate intestinal inflammation caused by Th17 effector CD4 + T cells. The need for additional immune suppression in the intestine reflects commensal microbe-driven T-cell activation through the accessory costimulation molecules ICOSL and OX40L. Eradication of commensal enteric bacteria mitigates intestinal inflammation and IL-17 production triggered by Treg depletion in B7-deficient mice, whereas re-establishing intestinal colonization with Candida albicans primes expansion of Th17 cells with commensal specificity. Thus, neutralizing B7 costimulation uncovers an essential role for Tregs in selectively averting intestinal inflammation by Th17 CD4 + T cells with commensal microbe specificity.

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A two-step, two-signal model for the primary activation of precursor helper T cells

Cited by 333 publications

References 59 publications

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

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A two-step, two-signal model for the primary activation of precursor helper T cells

Cited by 333 publications

References 59 publications

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 + T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

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Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2