Delayed-type hypersensitivity skin reactions are mediated by recirculating, sensitized Ly-I ÷ T cells (1, 2) that enter the tissues and are activated by specific antigen. This leads to the release of various nonspecific macromolecular mediators (lymphokines) that attract various leukocytes to leave the circulation and enter the tissues to comprise a characteristic infiltrate of inflammatory cells. In mice, this cellular recruitment requires that the activated T cells also activate resident tissue mast cells to release the vasoactive amine serotonin, which causes gaps to form between vascular endothelial cells (3 6). This allows the leukocytes to emigrate into the extravascular tissue spaces in response to chemattractant lymphokines (5, 6).The fact that T cell-dependent activation of mast cells is required for elicitation of delayed-type hypersensitivity led us to investigate whether a T cell product could mimic some of the functions of immunoglobulin E (IgE) antibody. We have described (7) a T cell-derived antigen-binding factor that transfers an immediate hypersensitivity-like reaction. In the present study this T cell factor was compared with a hybridoma |gE antibody. Both transferred sensitization for elicitation of immediatetype skin reactions with accompanying vascular permeability. Neither was active in mast cell-deficient mice. The T cell factor was distinguished from IgE by a number of immunochemical and biological properties; including affinity chromatography using specific anti-IgE and anti-factor antibodies, and a shorter duration of passive sensitization. The T cell factor is a suitable candidate for participation in the mechanism by which T cells activate mast cells in delayed-type hypersensitivity. Materials and MethodsMice. Male CBA/J and two types of mast cell-deficient mice, [WBB6F1 (WB-W/+ × C57BI6-WV/+)-W/W v and their normal litter mates (WBB6Fr+/+), and WCB6F1 (WC-SI/+ x C57BI/6-sId/+)-SI/S1 d and their normal litter mates (WCB6FI -+/+)] were obtained from The Jackson Laboratory, Bar Harbor, ME and were rested at least 1 wk in an air-filtered enclosure before use.Reagents. Picryl chloride (PCL) 1 (Chemotronix Inc., Swannonoa, NC) recrystalized three times from methanol/H20 before use, and oxazolone (OX) (Gallard-Schesinger Chemical Mfg.
Antigen-specific factors associated with immunosuppressive activity, released by cultured T cells from mice tolerant to the haptens trinitrophenyl, dinitrophenyl and oxazolone, were purified by hapten affinity chromatography. Their binding specificity for antigens paralleled their immunoregulatory activity. Like some immunoglobulin molecules, these factors had blocked NH2 termini and could be bound to Fc-like receptors on macrophages. However, neither immunoglobulin constant region determinants (isotypes) nor antigens encoded by the major histocompatibility complex were detected on the suppressive factors. The purified factors occurred as 68,000-dalton proteins and noncovalently linked dimers. No associated immunoglobulin light chain molecules were detected. The factors showed a marked propensity toward degradation with major breakdown products of 45,000-50,000 and 25,000-30,000 daltons. These results suggest that these molecules are the T-cell products analogous to B-cell immunoglobulin (equivalent to heavy chains) and that they may be the antigen-specific components which act in conjunction with major histocompatibility-controlled gene products to perform antigen-specific suppression.Central to our understanding of the mechanism by which lymphocytes respond to antigenic signals is elucidation ofthe nature of the surface membrane receptors for antigen. B and T cells, as part of their function, release soluble antigen-specific molecules that are capable ofeffector function (1, 2). B-cell-derived soluble effector molecules are immunoglobulins whose function in the immune system is dictated by their antigen binding specificity and the nature of the constant portion of the molecule. Although constant regions ofcirculating immunoglobulins may differ from those of their membrane-associated counterparts, the two forms of immunoglobulins express identical variable regions which perform binding functions. A similar situation obtains for at least some T lymphocytes. Antigen recognition at the cellular level is mediated by membrane receptors, and T-cell effector function is carried out by soluble antigen-specific products. However, although both cell-bound and soluble forms of T-cell antigen-binding molecules have been shown to bear antigenic determinants associated with immunoglobulin combining sites (idiotypes) (3), the overall structure of these molecules has yet to be clarified.As has been the case for B cells, detailed analysis of T-cell derived soluble antigen-specific effector molecules should illuminate the mechanisms by which T lymphocytes perform their effector function in the immune system. Moreover, although T cell-released soluble products may not be identical to T cell-membrane receptors for antigen, they provide a vehicle that can be used to clarify the nature of T cell-membrane receptors. In this report we describe the isolation and partial characterization ofT cell suppressor factors specific for dinitrophenyl (DNP), trinitrophenyl (TNP), or oxazolone (Ox). MATERIALS AND METHODSMaterials. Bovine ...
The genetic contro of the expression of an idiotype (Id-460) associated with the 2,4-dinitrophenyl (DNP)-binding BALB/c myeloma protein MOPC 460 was studied using congenic strains of mice. It was shown that the expression of high levels of Id-460 during secondary in vivo anti-DNP-ovalbumin responses was determined by genes governing immunoglobulin heavy-chain variable and kappa-light chain variable regions (V kappa). Appropriate alleles at both loci were required for the expression of Id-460. Genes in the major histocompatability complex and the X-linked immune deficiency gene found in strain CBA/N did not greatly affect Id-460 expression. The V kappa gene controlling Id-460 expression can be differentiated from Lyt-3, and it is the first instance in which expression of an idiotype subdivides the V kappa genes associated with the Lyt-3a allele. Although it is likely that the V kappa gene(s) involved are structural, the involvememt of a regulatory gene linked to the structural gene can not be excluded.
T cells that have been immunized to express optimal levels of contact hypersensitivity upon adoptive transfer to normal animals can be inhibited from doing so by incubating them with an antigen-specific T suppressor factor. This factor is composed of at least two subunits which come from cells expressing different Ly phenotypes; an antigen-specific antigen-binding "subfactor" is made by an Ly-1 cell and a non-antigen-binding one is made by an Ly-2 cell. Neither of these cells nor their products express detectable amounts of major histocompatibility gene products. The mode of immunization plays an important role in determining which of these subfactors will be produced. Painting the skin with a reactive hapten immunizes Ly-1 cells that secrete antigen-binding material, whereas intravenous injection of trinitrobenzenesulfonic acid activates Ly-2 cells to produce a second subunit that does not see antigen. There is reason to believe that the molecule that does not bind to antigen does have some antigen specificity. An analysis of the data at hand suggests that the antigen specificity stems from an interaction of the two subunits described with yet another subunit and that biological activity is dependent upon three macromolecules. Thus, the complex level of cellular interactions that regulate immunity may also be reflected in a similar type of complexity in the interaction between their biologically active cell-free products.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.