OX-40: life beyond the effector T cell stage.

The OX-40 receptor (OX-40R) is a transmembrane protein found on the surface of activated CD4(+) T cells. When engaged by an agonist such as anti-OX-40 antibody or the OX-40 ligand (OX-40L) during antigen presentation to T cell lines, the OX-40R generates a costimulatory signal that is as potent as CD28 costimulation. Engagement of OX-40R enhances effector and memory-effector T cell function by up-regulating IL-2 production and increasing the life-span of effector T cells. We hypothesize that the signal generated by the OX-40R inhibits activation-induced T cell death (AICD) and thereby increases the number of cells differentiating from the effector to memory T cell stage. In experimental autoimmune encephalomyelitis (EAE) OX-40R+ T cells are found only within the inflammatory site [central nervous system (CNS)]. Sorting OX-40R+ T cells from the CNS of animals with EAE revealed that they are autoantigen-specific T cells. Therefore, OX-40R-specific therapies were devised to eliminate or inhibit autoreactive T cells, while sparing the remainder of the T cell repertoire. In contrast, in vivo costimulation through the OX-40R in animals with cancer generated enhanced tumor-specific immunity leading to improved tumor-free survival. Thus, manipulation of the OX-40R during inflammatory responses can alter effector CD4(+) T cell function by enhancing or limiting T cell activation and survival.

Weinberg AD ，Vella AT ，Croft M 《SEMINARS IN IMMUNOLOGY》

Blocking OX-40/OX-40 ligand interaction in vitro and in vivo leads to decreased T cell function and amelioration of experimental allergic encephalomyelitis.

Weinberg AD ，Wegmann KW ，Funatake C ，Whitham RH ... -  《JOURNAL OF IMMUNOLOGY》

Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth.

Kjaergaard J ，Tanaka J ，Kim JA ，Rothchild K ，Weinberg A ，Shu S ... -  《CANCER RESEARCH》

Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses.

Gramaglia I ，Weinberg AD ，Lemon M ，Croft M ... -  《JOURNAL OF IMMUNOLOGY》

OX-40 antibody enhances for autoantigen specific V beta 8.2+ T cells within the spinal cord of Lewis rats with autoimmune encephalomyelitis.

Weinberg AD ，Lemon M ，Jones AJ ，Vainiene M ，Celnik B ，Buenafe AC ，Culbertson N ，Bakke A ，Vandenbark AA ，Offner H ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》