Effect of anti-CD3/anti-CD28/interleukin-2 stimulation of mononuclear cells on transforming growth factor beta inhibition of lymphokine-activated killer cell generation.
After simultaneous stimulation with anti-CD3 monoclonal antibody (mAb) at 10 ng/ml, anti-CD28 mAb at 125 ng/ml, and interleukin-2 (IL-2) at 20 U/ml, peripheral blood mononuclear cells (PBMC) were partially resistant to immunosuppression by transforming growth factor-beta (TGF beta 2). The doses of TGF beta 2 that inhibit cytotoxicity of IL-2 stimulated cells by 60%-70% were much less effective when the same cells were stimulated with anti-CD3/anti-CD28/IL-2. This favorable stimulation a generated a cell population characterized by high lytic activity, excellent expansion, and a greater resistance to immunosuppressive action of TGF beta 2. The secretion of secondary cytokines important for LAK generation is considered a crucial event, at least partially responsible for the antagonization of TGF beta immunosuppression.
Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J
J
Koberda
E A
EA
Grimm
R P
RP
Moser
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D017252:CD3 Complex / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive / Q000379:methods; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha