Antitumor Immunity and B Cells

The innate and adaptive arms of the immune system have the capacity to kill tumors. This cytolytic function is fulfilled by the innate immune system through NK cells and by the adaptive immune system through CD8 cytotoxic effector T cells (CTL). Initiation of anti-tumor immunity requires the participation of macrophages, dendritic cells and NK cells, all members of the innate immune system. The induction adaptive immunity and the generation of tumor specific CD8 T cell effector killers (CTL)...

AntiCD137Mediated Suppression of Humoral Immunity

Blocking the CD28 or CD40 costimulatory pathways using soluble ligands to CD80 CD86 or antibodies to CD154 suppresses the development of T cell dependent but not T-independent humoral immunity. Therefore, it was not surprising that we found that anti-CD137 mAbs also suppressed T-dependent but not T cell-independent B cell responses. What was surprising was that suppression was not mediated by blocking receptor-ligand binding but appeared to require CD137-mediated signaling. Classic T-dependent...

Immunization CD137 Breaks Ignorance and Tolerance

Agonistic anti-CD137 mAb need a certain degree of immunogenicity in the tumor in order to be able to exert their antitumor effects (Wilcox et al., 2002a). It became clear that transplantable tumors could be categorized into responsive and not responsive to anti-CD137 therapy, in a fashion that correlated with the intrinsic degree of immunogenicity of the tumor cells. It is still unknown if this basal immunization takes place upon presentation by endogenous dendritic cells (cross-presentation or...

Experimental Autoimmune Encephalomyelitis EAE

EAE is a primarily CD4+ T cell-mediated demyelinating disease of the CNS, and it is widely used as an animal model for human multiple sclerosis (MS). EAE can be induced in susceptible animal strains by immunization with various myelin proteins or immunodominant peptide epitopes derived from myelin basic protein (MBP), proteolipoprotein (PLP), or myelin oligodendrocyte glycoprotein (MOG) peptide emulsified in complete Freund's adjuvant (CFA) together with pertussis toxin treatment (Gonatas...

CD137 as an Adjuvant for Adoptive T Cell Therapy and Bone Marrow Transplantation

Adoptive transfer of antigen specific T lymphocytes is certainly a promising strategy for cancer treatment (Dudley and Rosenberg, 2003), as well as for chronic or latent viral infections (Moss and Rickinson, 2005). Several approaches are possible which share in common the obtainment of autologous lymphocytes that are stimulated with antigen in vitro and then artificially expanded for infusion. In these treatments interleukin-2 is commonly coadministered to keep injected lymphocytes alive and...

Significance of Reverse Signal Transduction for the Biology of the CD137 Receptor Ligand System

CD137 is a member of the TNF receptor family and it has originally been identified as a potent T cell costimulatory molecule. Recently, it has become evident that CD137 signals can also inhibit T cell activity under certain conditions. The CD137 receptor ligand system has the ability to signal bidirectionally. CD137 ligand is also expressed as a cell membrane protein and it can also transduce signals into the cells it is expressed on, referred to as reverse signaling. The signals through CD137...

Effects of CD137 Engagement on CD8 T Cells in vivo

Ligation of CD137 on naive T cells by CD137L or CD137 antibody in the absence of TCR signal does not induce detectable responses DeBenedette et al., 1997 Pollok et al., 1993 . Because naive T cells do not express detectable CD137 Cannons etal., 2001 Pollok et al., 1995 , it is thus possible that TCR is required for upregulation of CD137 on T cell surface. Studies of CD137 expression in vitro indicate that CD137 is expressed 24 h after activation with peak expression at 48-72 h Cannons etal.,...

CD137 Expression and T Cell Costimulation

CD137 is an activation inducible member of the TNFR superfamily and is found on activated thymocytes, T cells Kwon et al., 1994 Pollok et al., 1993 Schwarz et al., 1995 , and NK cells Melero et al., 1998b . It has recently been found on granulocytes Heinisch et al., 2000 , eosinophils Heinisch et al., 2001 , macrophages Kienzle and von Kempis, 2000 Langstein et al., 1998 , DC Futagawa et al., 2002 Pauly et al., 2002 Summers et al., 2001 Wilcox et al., 2002 , and within the intra-tumor...

CD137 Ligand Activities on Monocytes and Macrophages

CD137 ligand is expressed constitutively on peripheral monocytes and mono-cyte macrophage cell lines Table 3.2 . The signal through CD137 ligand activates monocytes and the CD137 lig-and signal alone is sufficient for activation. When CD137 ligand is crosslinked by recombinant CD137 protein or an anti-CD137 ligand antibody, it induces adherence of monocytes within a few hours. The adherent monocytes change their shape over the course of a week and adopt the three basic macrophage morphologies,...

CD137L Structure and Expression

CD137L is a 34 kD type II membrane glycoprotein with a carboxy-terminal extracellular domain and its gene is on chromosome 17 in the mouse Goodwin et al., 1993 . Although human CD137 ligand huCD137L is present in both T and B cells of the peripheral blood, the ligand is preferentially expressed in primary B cells and B cell lines. Daudi, a B cell lymphoma, is one of the B cell lines with the highest number of ligand molecules Zhou et al., 1995 . Scatchard analysis gave a kd of 1.4 x 10-9 M and...