Previous studies have demonstrated that progressive growth of the weakly immunogenic MCA 106 murine sarcoma stimulated, in the draining lymph nodes, the production of tumor-sensitized but not fully functional preeffector lymphocytes. These lymphocytes could develop into specific immune effector cells after sequential in vitro activation with anti-CD3 monoclonal antibody and interleukin 2 (IL-2)...

It is generally thought that during the contraction phase of an acute anti-viral T cell reponse, the effector T cells that escape activation-induced cell death eventually differentiate into central memory T cells over the next several weeks. Here we report that antigen-specific CD8T cells with the phenotype and function of central memory cells develop concomitantly with effector T cells during ...

The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in v...

Novel cellular therapies outside of traditional hematopoietic stem cell transplantation or hematopoietic progenitor cell (HPC) therapy are currently under evaluation in clinical trials across the United States and around the world. Several cellular products, e.g., CD19-directed Chimeric Antigen Receptor (CAR) T cells, are poised for FDA approval and thus increased use at a wider range of academ...

Transcription factors (TFs) are master gene products that regulate gene expression in response to a variety of stimuli. They interact with DNA in a sequence-specific manner using a variety of DNA-binding domain (DBD) modules. This allows to properly position their second domain, called "effector domain", to directly or indirectly recruit positively or negatively acting co-regulators including c...

Adenovirus-mediated transfection of mouse cardiac allografts with active human transforming growth factor-beta 1 (TGF-beta1) prolongs transplant survival provided that recipients are initially depleted of CD8+ T cells. To test if graft survival was prolonged by persistent TGF-beta1 transgene expression, long-term transfected allografts were re-transplanted into naïve mice that were transiently ...

Aim. To investigate pharmacological mechanisms of Wu Tou Tang acting on rheumatoid arthritis (RA) by integrating network analysis at a system level. Methods and Results. Drug similarity search tool in Therapeutic Targets Database was used to screen 153 drugs with similar structures to compositive compounds of each ingredient in Wu Tou Tang and to identify 56 known targets of these similar drugs...

The bacterial plant pathogen Pseudomonas syringae depends on a type III protein secretion system and the effector proteins that it translocates into plant cells to cause disease and to elicit the defense-associated hypersensitive response on resistant plants. The availability of the P. syringae pv. tomato DC3000 genome sequence has resulted in the identification of many novel effectors. We iden...

Antibody-mediated cellular cytotoxicity (ADCC), a key immune effector mechanism, relies on the binding of antigen-antibody complexes to Fcγ receptors expressed on immune cells. Antibodies lacking core fucosylation show a large increase in affinity for FcγRIIIa leading to an improved receptor-mediated effector function. Although afucosylated IgGs exist naturally, a next generation of recombinant...

Monoclonal antibody (mAb)-based therapeutics are the fastest growing class of human pharmaceuticals. They are typically IgG1 molecules with N-glycans attached to the N297 residue on crystallizable fragment (Fc). Different Fc glycoforms impact their effector function, pharmacokinetics, stability, aggregation, safety, and immunogenicity. Fc glycoforms affect mAbs effector functions including anti...