Feedback Inhibition of Specifically Sensitized Lymphocytes

Abstract

An explanation was sought for the fact that delayed-type hypersensitivity (DTH) does not normally occur in response to T-cell-dependent antigens unless an adjuvant is used. But when sheep red blood cells (SRBC) were administered intravenously DTH did appear, provided that the dose of antigen was less than that required to give a maximum antibody response. Animals in which T-cell activity had been blocked by a large dose of antigen could not be sensitized adoptively, and their spleen cells failed to transfer DTH to normal recipients. The serum of blocked animals partially inhibited the induction of DTH, and after absorption with SRBC its blocking activity increased substantially. Moreover, absorbed serum inhibited DTH in previously sensitized animals, but it did not inhibit the proliferative response to SRBC in peripheral lymph nodes or reduce the number of plaque-forming cells produced therein. On the contrary, the hemagglutinating titer was actually increased by blocking serum even though DTH was totally suppressed. It is concluded that a product of the interaction between antigens and antibody blocks the activated T cells which mediate DTH without interfering with helper cells.

Potentiation of T-Cell-Mediated Immunity by Selective Suppression of Antibody Formation With Cyclophosphamide

“…Cells from donor panel B were also used for transfer to CYtreated recipients which had been treated with CY (200 mg/kg) at intervals ranging from 0 to 5 days before cell transfer. As in a previous study (2), the transfer of one spleen equivalent of cells from untreated hypersensitive donors (group A) rendered recipients about half as sensitive as were the donors themselves (Fig. 3).…”

“…1). In fact, CY enhanced DTH only to the extent that it released the T-cell response from the feedback inhibition that normally accompanies the antibody response (2).…”

“…less responsive to SRBC (1,2). It was nonetheless apparent that DTH was potentiated because CY suppresses the inhibitory mechanism that is activated by a large dose of antigen.…”

The Immune Response of the Mouse to Lymphocytic Choriomeningitis Virus. II. Active Suppression of Cell-mediated Immunity by Infection with High Virus Doses

“…Similar patterns of immune responses are seen with other immunogens, for instance SRBC: low quantities induce in mice DTH but little antibody, whereas large quantities have the opposite effects (Mackaness et al, 1974). There is, however, a fundamental difference between both these systems, which makes us reluctant to directly apply knowledge obtained for the much better studied interaction between foreign red blood cells and mouse to the LCM virus-infected mouse.…”

STUDIES ON IMMUNE RESPONSES TO LARVAL CESTODES IN MICE. IMMUNOGLOBULINS ASSOCIATED WITH THE LARVAE OF MESOCESTOIDES CORTI

“…Using antigens such as sheep erythrocytes, fowl gammaglobulin and dinitrofluorohenzene in this assay, the response was shown to he highly T cell-dependent and could be transferred by sensitized cells hut not immune serum (Miller et ol., 1975). In order to detect reactivity against M. corti larvae, mice were treated with cyclopl~os~hamide, a procedure known to tempomrily reduce antibody production and to increase the DTH response (Turk, Parker and Poulter, 1972;Mackaness et al, 1974), and injected i.p., 2 days later, with 0.1 m1 of 1 : l mixture of packed peritoneal M. corti larvae and Freunds complete adjuvant (FCA) (Difco Laboratories, Detroit, Michigan, U.S.A.). Five days later, mice were challenged with 0.05 m1 of packed peritoneal larvae washed in PBS and injected into the footpad with a 23G needle.…”