title: Soluble factors in tolerance and contact sensitivity to DNFB in mice. X. IL-2 is the activation signal mediating release of synthesized suppressor factor.
abstract: Two signals are required for the in vitro activation of Lyt2+ T suppressor cells (Ts) from mice tolerized with 2,4-dinitrobenzene sulfonate (DNBS) to produce soluble suppressor factors (SSF) which suppress the transfer of contact sensitivity to dinitrofluorobenzene (DNFB). Recognition of DNP/class I MHC (signal one) stimulates the Ts to synthesize SSF. Release of SSF requires a soluble mediator (signal two) produced by the interaction of L3T4+ T cells from tolerant mice with I-A on metabolically functional cells in the DNP-presenting cell population. The purpose of this study was to examine the nature of this second Ts activation signal. Coculture of tolerant spleen cells and glutaraldehyde-fixed (Glu-) DNP-labeled spleen cells (DNP-SC) resulted in the synthesis but not release of SSF. Addition of either IL-1 or IL-2 to these cultures induced SSF release. Treatment of such cultured cells with the anti-murine IL-2 receptor antibody PC 61.5.3 blocked the IL-2- and IL-1-stimulated release of SSF. Release of SSF was also blocked when tolerant cells were cultured with (unfixed) DNP-SC in the presence of a monoclonal anti-IL-2 antibody. IL-2 but not IL-1 was able to stimulate the Ts to release synthesized SSF in the absence of L3T4+ TH activity. First, addition of IL-2 to cocultures of tolerant cells and DNP-presenting I-A- cells induced release of the synthesized SSF, whereas addition of IL-1 did not. Second, IL-2 also stimulated SSF release in cocultures of L3T4+ T cell-depleted tolerant cells and Glu-DNP-SC, whereas IL-1 did not. Tolerant cells pretreated with IL-2 and then washed were able to synthesize and release SSF upon culture with Glu-DNP-SC. Pretreatment of tolerant cells with IL-1 did not stimulate SSF release upon subsequent culture with Glu-DNP-SC. These results indicate that the Lyt2+ Ts from DNBS-tolerant mice express IL-2 receptors and IL-2 is the lymphokine which induces the Ts to release synthesized SSF. Thus, IL-2 provides a differentiative signal during the functional activation of these regulatory T cells.
authors.affiliation: Department of Microbiology/Immunology, University of Colorado School of Medicine, Denver 80262.
authors.forename: R L
authors.initials: RL
authors.lastname: Fairchild
authors.forename: J W
authors.initials: JW
authors.lastname: Moorhead
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000276:immunology*; D007108:Immune Tolerance; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013491:Suppressor Factors, Immunologic / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic; C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene