title: CD40 can costimulate human memory T cells and favors IL-10 secretion.
abstract: Optimal proliferation of T cells, although initiated via ligation of the CD3/TCR complex, requires additional costimulatory signals. While the most well-defined in vitro pathway of costimulation is via the B7 family of molecules, a large body of data clearly demonstrates an in vivo role for the CD40/CD154 pathway in transplantation, autoimmunity and allergy. We have examined the role of CD40 as an independent costimulatory molecule by generating a panel of transfected human fibroblasts expressing DR1 with either CD80, CD86 or CD40. Functional assays using allogeneic CD4(+) T cells as responders demonstrated that CD40 was capable of costimulating CD4(+) T cell proliferation particularly in the CD45RO subset. Costimulation by CD40 induced much higher levels of IL-10 than were induced by B7-expressing cells. On day 3 the dominant costimulation was provided by CD40, while by day 5 this was overshadowed by CD80 and CD86. Nonetheless, the provision of costimulation by CD40 was enough to expand an alloreactive T cell line. These results were confirmed in experiments using primary cultures of CD40(+)CD80/CD86(-) renal tubular epithelial cells as the stimulator population. Thus, CD40 is capable of functioning independently (in the absence of B7) as a costimulatory molecule both in terms of proliferation and cytokine release. The data have interesting implications concerning the consequences of antigen presentation by tissue parenchymal cells.
authors.affiliation: Department of Immunology, Imperial College of Science, Technology and Medicine, London, GB.
authors.forename: Nicola Jane
authors.initials: NJ
authors.lastname: Rogers
authors.forename: Ian Michael
authors.initials: IM
authors.lastname: Jackson
authors.forename: William James
authors.initials: WJ
authors.lastname: Jordan
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Alexandros
authors.initials: A
authors.lastname: Delikouras
authors.forename: Robert Ian
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D014162:Transfection
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D015798:HLA-DR1 Antigen; D008562:Membrane Glycoproteins; D016753:Interleukin-10