Chimeric antigen receptors (CAR) combine an antigen-binding domain with a CD3-zeta signaling motif to redirect T-cell specificity to clinically important targets. First-generation CAR, such as the CD19-specific CAR (designated CD19R), may fail to fully engage genetically modified T cells because activation is initiated by antigen-dependent signaling through chimeric CD3-zeta, independent of cos...

Immunosuppression is a prevalent clinical feature in chronic lymphocytic leukemia (CLL) patients, with many patients demonstrating increased susceptibility to infections as well as increased failure of an antitumor immune response. However, much is currently not understood regarding the precise mechanisms that attribute to this immunosuppressive phenotype in CLL. To provide further clarity to t...

BACKGROUND We intended to assess the intensity of apoptosis in the CD4+ and CD8+ T-lymphocytes of haemodialysis (HD) patients on recombinant human erythropoietin (rHuEpo). METHODS The expression of Fas, tumour necrosis factor-alpha receptors (TNFRI and TNFRII) and the CD28 molecule on lymphocytes was evaluated in 15 HD patients before and during treatment with rHuEpo. In cultures of periphera...

The adaptive immune system plays a critical role in protection at the time of secondary infection. It does so through the rapid and robust reactivation of memory T cells which are maintained long-term, in a phenotypically heterogeneous state, following their primary encounter with Ag. Although most HLA-A*0201/influenza matrix protein(58-66)-specific CD8 T cells from healthy donors display chara...

Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P < .001) and CD8 (P < .01) lympho...

PD-1, a member of the CD28 family of immune regulatory molecules, is expressed on activated T cells, interacts with its ligands, PD-L1/B7-H1 and PD-L2/B7-DC, on other cells, and delivers inhibitory signals to the T cell. We studied the role of this pathway in modulating autoreactive T cell responses in two models of myocarditis. In a CD8(+) T cell-mediated adoptive transfer model, we found that...

BACKGROUND CD4+ and CD8+ T lymphocytes are key regulators of postischemic neovascularization. T-cell activation is promoted by 2 major costimulatory signalings, the B7/CD28 and CD40-CD40 ligand pathways. Interestingly, CD28 interactions with the structurally related ligands B7-1 and B7-2 are also required for the generation and homeostasis of CD4+CD25+ regulatory T cells (Treg cells), which pla...

CD4 T cells are known to assist the CD8 T cell response by activating APC via CD40-CD40 ligand (L) interactions. However, recent data have shown that bacterial products can directly activate APC through Toll-like receptors, resulting in up-regulation of costimulatory molecules necessary for the efficient priming of naive T cells. It remains unclear what role CD4 T cell help and various costimul...