Differential inhibition of T and B cell function in IL-4-dependent IgE production by cyclosporin A and methylprednisolone.
The present study examines the role of the immunosuppressive agents methylprednisolone (MPN) and cyclosporin (Cs)A on IL-4-dependent IgE and IgG production. Addition of optimal amounts of IL-4 (100 U/ml) to cultures of tonsil mononuclear cells resulted in a mean increase in IgG production of 175% and in IgE production of 2460%. Frequency analysis of IgE- and IgG-producing B cells, using an ELISA spot assay, showed parallel increases in both Ig production and numbers of Ig-secreting B cells. IgE production was also enhanced by addition of IL-2 (10 U/ml) and maximal IgE production was obtained with a combination of IL-4 and IL-2. MPN (10(-7) M) and CsA (1 microgram/ml) markedly reduced IL4-induced IgE and IgG production as well as numbers of Ig-secreting cells in a dose-dependent fashion. The suppression of Ig production by the cyclosporins was restricted to the immunosuppressive compounds CsA, CsG, and dihydro-CsD, but not the nonimmunosuppressive drug CsH. Delayed addition of CsA revealed that inhibition was maximal when the drug was added during the first 48 h after addition of IL-4 to the culture. Addition of IL-2 (10 U/ml) partially overcame the inhibition induced by CsA. In coculture experiments, in which separated T or B cells were precultured with the drugs and the cells were then combined and further incubated in the presence of IL-4, the suppressive effects of CsA on IgE production were related to pretreatment of the T but not B cells. The maximum inhibiting effects of MPN were similarly observed when the drug was present in the cultures from the beginning, and addition of IL-2 also partially reversed this inhibition. In contrast to the results with CsA, pretreatment of the B but not T cells with MPN-reduced IgE production. These studies demonstrate that IL-4 increases both numbers of IgE-secreting cells as well as IgE production and CsA and MPN differentially affect the responding T and B cells, resulting in inhibition of Ig production.
Renz
H
H
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Mazer
B D
BD
Gelfand
E W
EW
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D003524:Cyclosporins; D007074:Immunoglobulin G; D007376:Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E; D008775:Methylprednisolone