@article {542556, title = {The B7 family revisited.}, journal = {Annu Rev Immunol}, volume = {23}, year = {2005}, month = {2005}, pages = {515-48}, abstract = {The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4+CD25+ T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cell-dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential.}, keywords = {Animals, Antigens, CD, Antigens, CD28, Antigens, CD80, Antigens, CD86, Antigens, Differentiation, Antigens, Differentiation, T-Lymphocyte, Asthma, Autoimmunity, CTLA-4 Antigen, Humans, Hypersensitivity, Inducible T-Cell Co-Stimulator Ligand, Inducible T-Cell Co-Stimulator Protein, Infection, Membrane Glycoproteins, Mice, Proteins, Transplantation Immunology}, issn = {0732-0582}, doi = {10.1146/annurev.immunol.23.021704.115611}, author = {Greenwald, Rebecca J and Freeman, Gordon J and Sharpe, Arlene H} }