CD28 molecule as a receptor-like function for accessory signals in cell-mediated augmentation of IL-2 production.
IL-2 production by PHA-stimulated MOLT 14 cells (a TcR gamma/delta-bearing human leukemic T cell line) and MOLT 16 cells (a TcR alpha/beta-bearing human leukemic T cell line) was markedly augmented by coculturing with BALL-1 cells ( a human leukemic B cell line), or with recombinant human interleukin-1 alpha (rhIL-1 alpha). We have previously shown that the augmentation of IL-2 production, induced by BALL-1 cells, requires cell to cell contact and is an IL-1-independent pathway. In this report, the expression of the CD28 molecule on MOLT 14 cells and MOLT 16 cells was examined for its role in IL-2 production augmented by BALL-1 cells. A 1-hr preincubation of MOLT 14 cells and MOLT 16 cells with anti-CD28 mAb resulted in the inhibition of BALL-1 cell-induced augmentation of IL-2 production (90 and 62% inhibition of control, respectively). The inhibition was observed in a dose-dependent manner of anti-CD28 mAb added and reached a plateau level at concentrations of 0.05 micrograms/ml of anti-CD28 mAb. This was sufficient to cover all the CD28 molecules expressed on the surface of both T cells as detected by flow cytometric analysis. Flow cytometric analysis also showed that the inhibition was not due to a modulation of CD28 molecules. In contrast, the treatment with anti-CD28 mAb did not inhibit IL-2 production which was augmented by rhIL-1 alpha costimulator. These results suggest that the CD28 molecule on the T cells is important for the interaction with BALL-1 cells which causes the augmentation of IL-2 production and further imply that the CD28 molecule is a receptor for an accessory signal provided by BALL-1 cells.
Kohno
K
K
Fujisaki Cell Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Shibata
Y
Y
Matsuo
Y
Y
Minowada
J
J
D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens; D002450:Cell Communication; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins