CD40 can costimulate human memory T cells and favors IL-10 secretion.
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.
Rogers
Nicola Jane
NJ
Department of Immunology, Imperial College of Science, Technology and Medicine, London, GB.
Jackson
Ian Michael
IM
Jordan
William James
WJ
Lombardi
Giovanna
G
Delikouras
Alexandros
A
Lechler
Robert Ian
RI
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
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