Active suppression of 1-fluoro-2,4-dinitrobenzene-immune T cells. Requirement of an auxiliary T cell induced by antigen.

Abstract

Shortly after the discovery of T-and B-cell interactions in humoral-immune responses, interest developed in the possible occurrence of interactions between T cells during cell-mediated-immune responses. T-T interactions occur in virtually all cellmediated-immune responses including graft-versus-host (GvH) 1 reactions (1), the development of cytotoxic T cells (2, 3), mixed lymphocyte reactions (4), responses to mitogens (5), generation of helper T cells (6, 7), and the development of delayed hypersensitivity (8). More recently, they have been discovered in the activation of suppressor T cells (T~) (9-11).The purpose of this study was to investigate whether T-T cell interactions were involved in the expression of suppressor T cells in contact sensitivity system. The results indicate that suppressor T cells, which block the efferent route of contact sensitivity (Ts-eff), require the presence of another population of auxiliary T suppressor cells (Ts-aux). The Ts-aux are present in populations of immune lymph node (LN) cells but not in populations of normal LN cells. Depletion of T,-aux, either by pretreatment with cyclophosphamide (Cy), anti-0 serum + C' treatment, or by adult thymectomy, rendered the immune LN cells (TDn) nonsuppressible by Ts-eff. Materials and MethodsMice. 2-to 4-mo-old female BALB/c mice were obtained from Simonsen Laboratories, Giiroy, Calif. CBA/J male mice were obtained from The Jackson Laboratory, Bar Harbor, Maine.Antigens and Tolerogens. 2,4-dinitrobenzene-1-suifonic acid sodium salt (DNBS) was obtained from Eastman Kodak Co., Rochester, N. Y. 2,4-dinitro-1-fluorobenzene (DNFB) was obtained

Antigen- and receptor-driven regulatory mechanisms. III. Induction of delayed type hypersensitivity to azobenzenearsonate with anti-cross-reactive idiotypic antibodies.

“…In contact sensitivity to DNFB, it was found that in order for DNP-specific suppressor T ceils to manifest their suppressive activities, the participation of another population of T cells termed auxiliary T cells (Ts-aux) is required. These T~-aux could be distinguished from TDn cells by their sensitivity to adult thymectomy and the presence of I-J region markers on the cell surface (38). It is possible that the interaction between T~ and T~-aux may be idiotype-specific whereas the expressed suppression is antigen specific, a notion similar in many respects to that discussed by Eardley et al (36).…”

Role of contrasuppression in the adoptive transfer of immunity.

“…Several laboratories have demonstrated that. low dose Cy treatment is effective in removing elements of suppressor T cell circuits (9)(10)(11). It is likely, therefore, that suppressor T cells are responsible for preventing adoptive transfer of the isolated immune population into normal recipients.…”

Novel Low Immunosuppressive Derivatives of the Antitumor Drug Fluoropyrimidine, UK-21 and UK-25: Effect on Delayed Type Hypersensitivity and Tumor Immunity

“…Rondinone et al (22) reported that CY-treatment of mice after sensitization with a higher dose of 1 x 108 SRBC enhanced the DTH response even though the response had been already aug mented by CY-pretreatment. They thought the most like ly target was the auxiliary cells to T suppressor cells of TDTH effector cells (26). The enhancement of 5 x 10' SRBC-DTH by FT-207 and 5-FU given after the sensitiza tion might occur through the same mechanism.…”