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PD-1 and its ligands in tolerance and immunity.
Current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential are discussed and an inhibitory bidirectional interaction between PD-L1 and B7-1 is discovered, revealing new ways the B7:CD28 family regulates T cell activation and tolerance.
Restoring function in exhausted CD8 T cells during chronic viral infection
It is found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the ‘helpless’ CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load.
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.
The B7 family revisited.
The roles of the B7:CD28 family members in regulating immune responses are revisited, and the therapeutic potential of these families is discussed.
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
The data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function.
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
These studies show overlapping functions of PD-L1 andPD-L2 and indicate a key role for the PD- L–PD-1 pathway in regulating T cell responses.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection
It is shown that exhausted CD8+ T cells are subject to complex layers of negative regulation resulting from the coexpression of multiple inhibitory receptors, and regulation of T cell exhaustion by various inhibitory pathways was nonredundant.
PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma.
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells
PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells, defining a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity.
CD4+CD25high regulatory cells in human peripheral blood.
Thymectomy in mice on neonatal day 3 leads to the development of multiorgan autoimmune disease due to loss of a CD(+)CD25(+) T cell regulatory population in their peripheral lymphoid tissues. Here,