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Elicitation of delayed-type hypersensitivity (DTH) responses is due to the required sequential action of two different antigen (Ag)-specific Thy-1+ cells: early acting, DTH-initiating cells and locally recruited CD4+, alpha beta-TCR+, DTH effector T cells. DTH-initiating cells have an unusual phenotype for Ag-specific cells (Thy-1+, CD5+, CD4-, CD8-, CD3-, sIg-, B220+ (CD45RA+), Mac 1+, IL-2R- and IL-3R+) and act by producing Ag-specific non-IgE factors that sensitize mast cells for release of the vasoactive amine serotonin (5HT) at the local site of elicitation of DTH by challenge. Another mechanism of DTH initiation involves Ag-specific IgE antibodies that also can sensitize mast cells for local serotonin release. Serotonin initiates DTH by activating the local endothelial cells to allow recruitment of DTH effector T cells, and also by activating 5HT-2 receptors on these recruited T cells.

The recent identification of a T-cell-derived antigen-binding molecule (TABM), Trichinella spiralis factor (Tric-F), isolated from culture supernatants of lymphoid cells from mice infected with the intestinal helminth T. spiralis, has led to investigation of the ability of Tric-F to induce a T-cell-dependent feedback circuit that ultimately suppresses the production of other TABMs with similar (isotype-like) features. This form of regulation that has been identified in contact hypersensitivity and in delayed-type hypersensitivity (DTH) responses to tumor cells, was shown not to be antigen-specific but to be DTH-specific. Injection of mice with the TABM called picryl chloride factor (PCl-F) induced suppression of the production of DTH-initiating TABMs of other antigenic specificities. In this study, we report that intravenous injection of mice with Tric-F or PCl-F, 8 days before an oral infection with T. spiralis, induced suppressor cells that inhibited the T-cell-dependent influx into the gut of inflammatory cells, comprising mast cells and eosinophils. Similar results were obtained when the mice were skin sensitized with PCl 8 days prior to a T. spiralis infection, i.e. in a system where TABMs are known to be produced. The phenotype of these suppressor cells was Lyt-1-2+. This suppression preferentially affected the parasite-induced DTH-like response in the gut. In contrast, increased levels of IgA plasma cells in the gut, and worm expulsion were not affected by these treatments. In reciprocal experiments, intravenous injection of Tric-F, or PCl-F, or an oral infection with T. spiralis (that results in the production of TABMs) given 8 days before contact sensitizing mice with PCl, resulted in a suppression of elicitation of cutaneous DTH, as measured by ear swelling. In contrast, pretreatment with anti-dinitrophenyl IgE antibody did not interfere with intestinal inflammation to T. spiralis nor with DTH to PCl. Our results suggest that similar to cutaneous DTH, T. spiralis-specific T-cell factors are involved in the initiation and regulation of the DTH-like mast cell and eosinophil-rich intestinal inflammation that accompanies T. spiralis infections in the gut. Since both Tric-F and PCl-F induce suppression of cellular immune responses in vivo, independent of antigen specificity, it is concluded that Tric-F belongs to the same isotype of TABMs as PCl-F that therefore can be regulated by a non-antigen-specific, isotype-like, T-cell-dependent feedback mechanism.

Immunochemical and biological characterization was performed of an antigen-binding factor derived from culture supernatants of T cells from mice infected 4 days previously with the intestinal helminth Trichinella spiralis. Affinity chromatography with T. spiralis antigen resulted in the purification of a protein, provisionally designated Trichinella factor (Tric-F), that shared antigenic and other properties with a known T-cell-derived antigen-binding factor of different antigenic specificity, picryl chloride factor, which mediates an early 2-hour component of contact sensitivity. Tric-F lacked determinants of immunoglobulins and possessed determinants shared by other antigen-specific T cell factors, as determined by ELISA and antibody affinity chromatography. Biological activity of Tric-F was assayed in vivo and in vitro. Mice injected intravenously with Tric-F developed an antigen-specific early 2-hour ear swelling response following local challenge with T. spiralis antigen. These results corresponded to delayed-type hypersensitivity responses in the ears of T. spiralis-infected mice that comprised early 2-hour and late classical 24-hour responses. In vitro, Tric-F induced serotonin release by mast cells in the presence of T. spiralis antigen. Mast cells sensitized with Tric-F formed rosettes with antigen-coated sheep erythrocytes. It is suggested that Tric-F, an antigen-binding molecule that is T-cell-derived, mediates the early 2-hour component of delayed-type hypersensitivity and is involved in the initiation and regulation of T-cell-mediated intestinal inflammation during a T. spiralis infection in mice.

We have studied the specificity of macroscopic responses and the corresponding cellular infiltrates in Giemsa-stained, glycol methacrylate embedded tissue sections of delayed skin reactions elicited by contact sensitizers, homologous and heterologous hapten-protein conjugates, and tuberculin (PPD) in guinea pigs. The animals were sensitized with contact sensitizers emulsified in Freund's complete adjuvant and tested at 19 days and, after repeated contact testing with homologous sensitizer, at 48 days after sensitization. At both times, all delayed reactions contained numerous mononuclear cells. The reactions elicited by contact sensitizer or hapten-protein conjugate also contained significant numbers of basophils which were lacking in PPD reactions. Contact reactions were highly specific macroscopically and microscopically while reactions elicited by conjugates displayed considerable macroscopic and microscopic cross-reactivity. The greater cross-reactivity of conjugate-elicited reactions compared to contact reactions may reflect differences in mechanism of initiation or mediation of these two reactions.