The expanding B7 superfamily: Increasing complexity in costimulatory signals regulating T cell function

  title={The expanding B7 superfamily: Increasing complexity in costimulatory signals regulating T cell function},
  author={Anthony J Coyle and José Carlos Gutiérrez-Ramos},
  journal={Nature Immunology},
Upon encounter with specific antigen, naïve T helper precursor (THP) cells become activated. This event is regulated not only by engagement of the T cell receptor (TCR) with peptide presented in the context of major histocompatibility complex (MHC) class II molecules but by a number of costimulatory signals. CD28 engagement by B7-1 and B7-2 on resting THP cells provides a critical signal for initial cell cycle progression, interleukin 2 production and clonal expansion. However, largely as a… 
Inducible Costimulatory Molecule-B7-Related Protein 1 Interactions Are Important for the Clonal Expansion and B Cell Helper Functions of Naive, Th1, and Th2 T Cells 1
It is shown that ICOS signaling is involved in the initial clonal expansion of primary and primed Th1 and Th2 cells in response to immunization, and while ICOS-B7RP-1 interactions have no effect on the migration of T cells into B cell follicles, it is essential for their ability to support B cell responses.
The role of ICOS and other costimulatory molecules in allergy and asthma
The role of costimulatory signals, which include CTLA-4, PD-1 and the recently described Ig superfamily members BTLA and TIM-3, in the pathogenesis of asthma and allergic responses is discussed.
Interaction of B7RP-1 with ICOS Negatively Regulates Antigen Presentation by B Cells
The B7RP-1/ICOS pathway is negatively regulating T cell activation by B cells and may play a role similar to that of the PD-L1/PD-1 pathway.
T lymphocytes express B7 family molecules following interaction with dendritic cells and acquire bystander costimulatory properties
Evidence is obtained that DC, in the absence of any foreign antigens, induce the expression of B7 family costimulatory molecules, such as CD80, CD86, B7‐H1, PD‐L2, B 7‐H3, and B7RP‐1, on autologous T lymphocytes.
The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens
It is shown that initiation of T cell responses requires the expression of B7 on immunizing APCs, but the responses are much greater in the absence of basal B7 expression, thereby inducing autoimmunity.
T‐cell costimulatory pathways in allograft rejection and tolerance
The functions of the CD28:B7 and the tumor necrosis factor receptor (TNFR) family of molecules in allograft rejection and tolerance and the important and unique interactions between the various pathways are discussed.
Modification of accessory molecule signaling
  • M. Crow
  • Biology, Medicine
    Springer Seminars in Immunopathology
  • 2006
Significantly for patients with autoimmune diseases, the manipulation of costimulatory signals represents a rational and effective approach to modulating the chronic immune system activation that characterizes those diseases.
Harnessing negative T‐cell costimulatory pathways to promote engraftment
  • J. Popoola, M. Sayegh
  • Biology
    Transplant international : official journal of the European Society for Organ Transplantation
  • 2008
Examination of the molecular interaction that occurs when a lymphocyte encounters an antigen-presenting cell has revealed that T cells require multiple signals to become fully activated and the discovery that co-stimulatory signals maybe positive or negative, and that it is the interplay between these pathways that determines the ultimate outcome of the immune response in-vivo.
Costimulatory Molecules and Autoimmune Thyroid Diseases
The absence of B7 and ICAM-1 antigens in most GD TFC may more easily be associated with anergy and apoptosis of infiltrating T-cells, preventing the perpetuation and expansion of a "destructive" autoimmune reaction.
Roquin: a novel immune regulator that represses ICOS expression and differentiation of self-reactive T cells
The cellular and molecular mechanisms that may explain how Roquin’s regulation of ICOS can contribute to repress organ-specific and systemic autoimmunity are discussed.


B7-H3: A costimulatory molecule for T cell activation and IFN-γ production
A newly identified member of the human B7 family, designated B7 homolog 3 (B7-H3), that shares 20–27% amino acid identity with other B7family members is described, that may participate in the regulation of cell-mediated immune responses.
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.
Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation
It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.
ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28
The identification of a third member of this family of molecules, inducible co-stimulator (ICOS), which is a homodimeric protein of relative molecular mass 55,000–60,000 (Mr 55K–60K) indicates that ICOS is another major regulator of the adaptive immune system.
Differential T cell costimulatory requirements in CD28-deficient mice.
CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.
ICOS is essential for effective T-helper-cell responses
In vivo genetic evidence is provided that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens.
T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression.
It is shown that the CD28 molecule synergizes with protein kinase C activation to induce IL-2 gene expression and can cause vigorous T-cell proliferation even in the presence of cyclosporine, and that cyclospora does not prevent transcription of 16-2 mRNA, as has been suggested previously.
ICOS is critical for CD40-mediated antibody class switching
Mice lacking ICOS exhibit profound deficits in immunoglobulin isotype class switching, accompanied by impaired germinal centre formation, and class switching was restored in ICOS-/- mice by CD40 stimulation, showing that ICOS promotes T-cell/B-cell collaboration through the CD40/CD40L pathway.
ICOS co-stimulatory receptor is essential for T-cell activation and function
It is shown that T-cell activation and proliferation are defective in the absence of ICOS, and ICOS-/- mice showed greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that ICOS has a protective role in inflammatory autoimmune diseases.