Immunoregulatory role of transforming growth factor beta (TGF-beta) in development of killer cells: comparison of active and latent TGF-beta 1.
Using recombinant DNA technology, we have generated Chinese hamster ovary (CHO) cell lines that synthesize latent transforming growth factor beta 1 (TGF-beta 1) to study immune regulation by TGF-beta 1. In vitro, latent TGF-beta 1 synthesized by transfectants or added exogenously as a purified complex after activation inhibited CTL generation to a similar extent as seen with acid-activated recombinant human (rHu) TGF-beta 1. In vivo, serum from nu/nu mice bearing CHO/TGF-beta 1 tumors contained significant levels of latent TGF-beta 1 in addition to depressed natural killer (NK) activity in spleens which paralleled that seen in C3H/HeJ mice treated with acid-activated rHuTGF-beta 1. rHuTGF-beta 1 treatment of mice receiving heart allografts resulted in significant enhancement of organ graft survival. Because of possible regulated tissue-specific activation, administration of latent rather than active TGF-beta may provide a better route to deliver this powerful immunosuppressive agent in vivo.
Wallick
S C
SC
Department of Immunology Research and Assay Technologies Genetech, Inc., South San Francisco, California 94080.
Figari
I S
IS
Morris
R E
RE
Levinson
A D
AD
Palladino
M A
MA
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010053:Ovary; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta