Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells
| Autor: | Stephen J. Galli, G L Weitzman, Y A Mekori |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Cellular immunity
medicine.medical_specialty Reserpine T cell T-Lymphocytes Immunology Biology Dermatitis Contact Lymphocyte Activation T-Lymphocytes Regulatory chemistry.chemical_compound Mice Immune system In vivo Internal medicine Idoxuridine medicine Immunology and Allergy Animals Mast Cells Mice Inbred BALB C Immunization Passive Articles Mast cell Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Delayed hypersensitivity Female Lymph Nodes Histamine Immunosuppressive Agents Injections Intraperitoneal medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), thereby preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. We therefore decided to reevaluate the mechanism by which reserpine abrogates expression of cellular immunity, and investigated whether the drug might interfere with T cell activity in vitro or in vivo. At concentrations as low as 4 microM, reserpine profoundly suppressed baseline or antigen-augmented levels of [3H]thymidine incorporation by immune lymph node cells obtained from mice sensitized to the contactant oxazolone [I-LNC(Ox)]. This effect was observed both with I-LNC derived from normal mice and with I-LNC derived from congenitally mast cell-deficient W/Wv mice, cell preparations that lacked detectable mast cells, histamine, and 5-HT. Furthermore, treatment of I-LNC with reserpine (20 microM) for 1 h in vitro virtually abolished the ability of these cells to transfer CS to naive mice. This was not a cytolytic effect, as the viability of the I-LNC treated with reserpine was not affected, and washing of the reserpine-treated I-LNC before transfer fully restored their ability to orchestrate a CS response. The action of the drug was not mediated by an effect on mast cells, since the experiment could be performed using mast cell-deficient W/Wv mice as both donors and recipients of I-LNC. In addition, the effect was specific for the treated cells: mice that received reserpine-treated I-LNC(Ox) intravenously together with untreated I-LNC(DNFB) did not develop CS to Ox but responded normally to DNFB; and local intradermal injection of reserpine-treated I-LNC(Ox) which failed to transfer reactivity to Ox, did not interfere with the development of CS to DNFB at the same site. Finally, cotransfer experiments indicated that the effect of reserpine on the transfer of CS was not due to activation of suppressor cells. Our findings strongly suggest that whatever effects reserpine might have on immunologically nonspecific host cells, the drug's effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo. |
| Databáze: | OpenAIRE |
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