Role of B7 signaling in the differentiation of naive CD4+ T cells to effector interleukin-4-producing T helper cells

  title={Role of B7 signaling in the differentiation of naive CD4+ T cells to effector interleukin-4-producing T helper cells},
  author={William C. Gause and Joseph F. Urban and Peter S. Linsley and Ping Lu},
  journal={Immunologic Research},
Signaling through the T cell receptor must be accompanied by costimulatory signals for the differentiation of naive T cells to cytokine-producing effector T helper cells. The costimulatory signal through CD28 is required for T cell activation resulting in increased interleukin (IL)-2 production in vitro, but its role in the production of IL-4 and in the in vivo response is still unclear. We have examined the effects of blocking CTLA-4 (the CD28 homologue) ligand interactions on the in vivo… 

The development of CD4+ T effector cells during the type 2 immune response

The type 2 response to infectious pathogens is pronounced in CD28-/-mice, suggesting that other costimulatory molecule interactions can substitute for CD28 for the development of IL-4 producing T cells and the associated type 2 immune response.

CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-helper cell differentiation after inhaled allergen.

Analysis of cytokine gene expression revealed that T cells from CD28-deficient mice failed to differentiate into Th2 cells in either the presence or absence of B7-dependent signals, and therefore did not recruit eosinophils to the airway.

The Role of Costimulatory Molecules in the Development of Memory and Effector T Helper 2 Cells During an in vivo Immune Response to the Murine Gastrointestinal Parasite Heligmosomoides polygyrus

The effects of costimulatory molecule blockade on T helper effector cell function during the memory response were examined and the role of OX40L in Ag-specific CD4+ T cell IL-4 production following priming was examined.

B7-2 is required for the progression but not the initiation of the type 2 immune response to a gastrointestinal nematode parasite.

It is demonstrated that B7-2 interactions are not necessary for the initiation of the type 2 immune response, but are instead required for its progression after the development of effector T cells.

A key role for ICAM-1 in generating effector cells mediating inflammatory responses

Interactions of lymphocyte function–associated antigen 1 with ICAM-1 during priming induce both qualitative and quantitative alterations in T effector function and induce potentially autodestructive responses.

Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells.

At the level of naive CD4(+) cells, anergy induction appears to reflect selective contact with APC expressing ICAM-1 in the absence of B7, and conspicuous induction of anergy occurred after T cell culture withAPC expressing MHC class II and intercellular adhesion molecule-1 (ICAM- 1).

Requirements for the development of IL‐4‐producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo

Part of the type 2 immune response may mediate host protection against both helminthic parasites and harmful allergic responses and this model system avoids possible parasite antigen‐specific T‐cell clones or cross‐reactive memory T cells that may preferentially differentiate into Th2 effector cells during the course of infection.

Essential Role for Both CD80 and CD86 Costimulation, But Not CD40 Interactions, in Allergen-Induced Th2 Cytokine Production from Asthmatic Bronchial Tissue: Role for αβ, But Not γδ, T Cells

It is demonstrated that ex vivo allergen stimulation of bronchial biopsy tissue from mild atopic asthmatic, but not atopic nonasthmatic, subjects induced production of IL-5, IL-4, and IL-13, and costimulation by both CD80 and CD86 appears to be the principal costimulatory molecule required in PBMC responses.

p38 alpha mitogen-activated protein kinase is activated by CD28-mediated signaling and is required for IL-4 production by human CD4+CD45RO+ T cells and Th2 effector cells.

P38 alpha plays an important role in some, but not all, CD28-dependent cellular responses, and its preferential involvement in IL-4 production by CD4+CD45RO+ T cells and Th2 effector cells suggests that p38 alpha may be important in the generation of Th2-type responses in humans.

T-cell Subset Regulation in Atopy

The understanding of the T-cell subset reciprocal interaction in atopy is discussed, including Th17 and Th9 cells, which control local tissue inflammation through upregulation of proinflammatory cytokines and chemokines.



CTLA-4 ligands are required to induce an in vivo interleukin 4 response to a gastrointestinal nematode parasite

Results suggest that stimulation of CD28 and/or CTLA-4 is required for T cell priming leading to IL-4 cytokine production, B cell activation, and IgE secretion during a Th2-like, mucosal immune response to a nematode parasite.

CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical role in T cell priming for IL-4 and interferon gamma production

IL-2 plays a critical role in priming naive CD4+ T cells to become IL-4 or IFN-gamma producers and engagement of the CD28 pathway, although normally important in such priming, is unnecessary in the presence of exogenous IL-2.

Requirement of CTLA-4 counter receptors for IL-4 but not IL-10 elevations during a primary systemic in vivo immune response.

The results suggest that, with the notable exception of IL-10, interaction, of B7 with its ligands is required for elevated Th2 cytokine gene expression and secretion during a primary systemic IL-4-dominant response.

CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4

It is demonstrated that engagement of CD28 on Th2 cells with anti-CD28 antibody or with APC-associated B7 costimulates Th2 responsiveness to IL-4 but does not affect IL- 4 or IL-2 production by Th2 Cells.

CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells.

Like anti-CD28 mAb, autologous human APC appeared to stimulate a cyclosporine A-resistant pathway of T cell activation and suggest that the two signals required for IL-2 production by CD4+ T cells can be transduced by the TCR and CD28.

Role of IL-6, IL-1, and CD28 signaling in responses of mouse CD4+ T cells to immobilized anti-TCR monoclonal antibody.

The interaction of IL-6, IL-1, and CD28 signaling in the activation of mouse CD4+ T cells is explored, and the results suggest that, depending on the nature of the TCR stimulus, T cell activation may also require additional co-stimulatory signals provided by cytokines.

Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.

It is demonstrated that the murine B7 (mB7) protein is a potent costimulatory molecule for the activation of resting murine CD4+ T cells through the T-cell receptor (TCR)/CD3 complex, and the combination of a calcium ionophore and phorbol 12-myristate 13-acetate (PMA) stimulates T cells efficiently.

Activated human B lymphocytes express three CTLA-4 counterreceptors that costimulate T-cell activation.

It is shown that activated human B lymphocytes express two additional CTLA-4 counterreceptors also capable of providing T-cell costimulation, which are likely to be essential for generation of an immune response and their absence may result in antigen-specific tolerance.

IL-4 production by T cells from naive donors. IL-2 is required for IL-4 production.

The results suggest that the bulk of IL-4 production by T cell populations, from normal mice, in response to anti-CD3 depends upon cells that are already activated and that IL-2 is required for such production.

CD27 is a signal-transducing molecule involved in CD45RA+ naive T cell costimulation.

It is demonstrated that the CD27/CD70 interaction induces costimulatory signals in T cells, especially CD45RA+ naive T Cells, indicating that CD27 serves as a T cell signal-transducing molecule.