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Requirements for Induction of T Cell Tolerance to Dnfb: Efficiency of Membrane-Associated DNFB¹

Division of Clinical Immunology, Departments of Medicine and Microbiology, University of Colorado School of Medicine, Denver, Colorado 80220

Abstract

Tolerance to contact sensitization with DNFB,³ a T cell-dependent phenomenon, was induced in mice by preparations of DNFB coupled to mouse RBC or spleen cells. Such tolerance is dose related, wanes with time, and can be transferred to normal animals with lymphoid cells (presumably containing suppressors). Tolerance to DNFB-RBC can be produced by whole DNFB-RBC, by ghosts of these cells, by sonicates of the ghosts, and by detergenttreated DNFB-RBC ghosts. Tolerance cannot be produced by larger amounts of DNFB-RBC components not associated with membrane. The ability of various DNP compounds to stimulate DNA synthesis in DNFB-sensitized cells also correlates with their ability to bind to protein components; i.e., DNFB is a far more efficient stimulator than DNBSO₃, whereas DNP-lysine does not stimulate at all. Thus, the ability to sensitize or to tolerize with DNFB congeners is related to their ability to couple to proteins. It appears that the active induction of T cell tolerance requires that tolerogen be coupled to cell membranes. Since both T cell sensitization and tolerance to DNFB are best produced by DNFB-membrane, the actual occurrence of one state or the other must depend on the molecular method of "presentation" of DNFB-membrane.

Footnotes

¹ This work was supported in part by National Institutes of Health Grants AI-12685 and AI-TI-13. Dr. Miller is a postdoctoral trainee of the United States Public Health Service.

³ Abbreviations used in this paper: DNFB, 2,4-dinitro-1-fluorobenzene; RBC, red blood cells; DNP, 2,4-dinitrophenol; TNCB, picryl chloride; DNBSO₃, 2,4-dinitrobenzene-1-sulfonic acid; PBS, phosphate-buffered saline; HBSS, Hanks' balanced salt solution; SDC, sodium deoxycholate, SC, spleen cells; TCA, trichloroacetic acid, ³H-Tdr, ³H-thymidine, PHA, phytohemagglutinin.

² Reprint requests should be addressed to Henry N. Claman, M.D., Division of Clinical Immunology, Box B164, University of Colorado Medical Center, Denver, Colorado 80220.