The Role of TNF Receptor and TNF Superfamily Molecules in Organ Transplantation

Abstract

The rapid increase in the number of molecules demonstrated to regulate immune responses has provided new opportunities for manipulation of the recipient immune response to transplanted organs. Molecules belonging to the TNF receptors and TNF superfamily are increasingly recognized as playing a major role in the regulation of immune responses to tumor, viral, and autoantigens. The mechanisms by which these molecules regulate immune responses are diverse. TNF receptor-related molecules have been shown to control the development of secondary lymphoid organs, affect the activation and survival of T cells and antigen presenting cells, and alter cytokine and chemokine production. An increasing amount of data suggest that some TNFR superfamily members are particularly important for the function of CD8 π T cells. Based on our current understanding of these molecules it seems highly likely that strategies that target selected TNFR/ TNF superfamily molecules will be useful for controlling or preventing the rejection of transplanted organs and tissues.

Interaction Between ICOS-B7RP1 and B7-CD28 Costimulatory Pathways in Alloimmune Responses In Vivo

“…Recently a number of novel receptor-ligand pairs have been described that act as efficient T-cell costimulatory molecules (7,8). These include members of the B7-CD28 family such as inducible costimulator (ICOS) and its ligand B7RP1, as well as members of the TNF superfamily (8,9). The large number of such costimulatory molecules results in a complex network of potential interactions and interdependence, of which we still understand relatively little, but which may have profound effects on how we attempt to utilise these pathways therapeutically.…”

How Can We Measure Immunologic Tolerance in Humans?

“…Early examples of co-stimulatory molecules that are expressed by T cells include CD28 and its ligands CD80 and CD86 and CD154 and its ligand CD40. Subsequently, a number of additional co-stimulatory molecules (4-1BB and OX40), many of which belong to the TNF receptor superfamily, have been described (reviewed in reference [17]). T cell anergy can result when antigen is recognized without co-stimulatory signaling.…”

Role of 4-1BB in Allograft Rejection Mediated by CD8+ T Cells

“…Although numerous studies have examined the role of TNFR SF molecules in autoimmune, viral, and neoplastic diseases, relatively little is known about the role of TNFR SF molecules other than CD40 in the host response to allogeneic organs and tissues [reviewed (6)]. These studies are complicated by the broad cellular distribution of TNF/TNFR SF molecules and the ability of certain receptor/ligand pairs to bind more than one partner with high affinity.…”