Inhibition of IL-2-dependent proliferation by a prostaglandin-dependent suppressor factor.
In the picryl chloride contact sensitivity system in mice, i.v. injections of trinitrobenzene sulfonic acid (TNBSA) prevents elicitation of delayed-type hypersensitivity reactions. This suppression is due in part to a non-specific, PG-dependent factor (TNBSA-F) that is induced by i.v. injection of TNBSA and is produced by pooled spleen and lymph node cells in vitro. Inasmuch as a role for lymphokines such as IL-2 has been postulated in delayed-type hypersensitivity, we determined the in vitro effects of TNBSA-F on the responsiveness of HT-2 target cells to IL-2. TNBSA-F induced a dose-dependent unresponsiveness of HT-2 cells to IL-2. The inhibitory activity was not present in supernatants from lymphoid cells of sham-treated mice. In the presence of indomethacin, spleen, and lymph node cells from TNBSA-immunized mice produced a factor whose activity was much reduced compared to TNBSA-F. This suggested that PG were required for TNBSA-F activity. However, PG alone did not induce the unresponsiveness because TNBSA-F but not sham-treated mice had inhibitory activity despite containing similar levels of PGE2. Rather, the combination of i.v. TNBSA injections and PG synthesis during production of TNBSA-F were required to produce a suppressive TNBSA-F. The inhibitory effect of TNBSA-F was not due to the presence of transforming growth factor-beta, soluble immune-response suppressor, INF-gamma, or JE in the factor preparation. Partial characterization showed a single peak of in vitro TNBSA-F activity (molecular mass approximately 35-55 kDa) by Sephadex G-200 gel filtration chromatography and by HPLC. In addition, TNBSA-F retained its activity after multiple cycles of freeze-thaw and heating for 1 h at 56 degrees C. The inhibitory effects of TNBSA-F on IL-2-induced proliferation suggest that suppression of delayed type hypersensitivity after i.v. administration of TNBSA may, in part, be due to a PG-dependent suppressor factor that inhibits the responsiveness of target cells to IL-2.
Ferreri
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Department of Medicine, Yale University School of Medicine, New Haven, CT 06510.
Herzog
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Askenase
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PW
D000818:Animals; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D005260:Female; D007213:Indomethacin / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011453:Prostaglandins / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D016212:Transforming Growth Factor beta; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D007376:Interleukin-2; D011453:Prostaglandins; D013491:Suppressor Factors, Immunologic; D016212:Transforming Growth Factor beta; C013256:soluble immune response suppressor; D014302:Trinitrobenzenesulfonic Acid; D007213:Indomethacin