Abstract Effects of tolerogenic form of bovine γ-globulin (BGG) on the Jones-Mote hypersensitivity, tuberculin hypersensitivity, and helper function were studied in guinea pigs. 1) When intermediate or large doses of tolerogenic BGG were injected i.v. on day -14 or 0 and immunogenic BGG in complete Freund's adjuvant (CFA) was injected subcutaneously on day 0, tuberculin hypersensitivity and helper function were depressed, although Jones-Mote hypersensitivity was preserved or augmented. Jones-Mote hypersensitivity was suppressed with the uppermost dose of tolerogenic BGG. Suppressing mechanism(s) to Jones-Mote hypersensitivity appears to be slightly more resistant to tolerance induction than tuberculin hypersensitivity and helper function and more sensitive than Jones-Mote hypersensitivity. 2) Expression of tolerant states was not absolute but relative to the doses of immunogenic BGG. When a larger amount of immunogenic BGG was given, larger amounts of tolerogenic BGG were required to obtain the same degrees of tolerance as that expressed in animals given a smaller amount of immunogenic BGG. 3) In animals in which immune responses were suppressed partially with tolerogenic BGG, tuberculin or Jones-Mote hypersensitivity was delayed in the development. 4) Basophils comprised more than half of the infiltrating cells at the sites of erythematous reactions elicited in the animals showing the tolerant states of tuberculin hypersensitivity and helper function. Thus, typical Jones-Mote hypersensitivity was raised preferentially in the tolerant states of other types of immune responses. These findings may be explained by different affinities to BGG among T cell subpopulations responsible for individual responses and individual cells within a subpopulation for each response.
Abstract We investigated NK cell infiltration into tumor developing lesions at early stage of tumor development after intraperitoneal inoculation of 3LL lung carcinoma into syngeneic C57BL/6 mice. Natural killer (NK) cells, which were detected by anti‐NK 1.1 monoclonal antibody (mAb), remarkably increased in number in tumor‐developing lesions (peritoneal cavity) as early as day 3 after inoculation of 3LL. The tumor‐infiltrating NK cells from 3LL‐inoculated mice produced a high level of interferon‐γ by co‐culture with 3LL and showed enhanced cytotoxic activities against both NK‐sensitive (YAC‐1) and NK‐resistant (3LL and P815) tumors. Furthermore, mice depleted of NK cells by injection of anti‐NK 1.1 mAb or antiasialo GM1 antibody showed shorter survival times after intraperitoneal inoculation of 3LL when compared with control mice. These results suggest that NK cells infiltrate the tumor‐developing lesion at an early stage and may participate in the early protection against tumors through production of a high amount of interferon‐γ and enhanced cytotoxicity at tumor‐bearing sites.
Most T cells develop through the thymus, where they undergo positive and negative selection. Some peripheral T cells are known to develop in the absence of thymus, but there is insufficient information about their selection. To analyze the selection of extrathymically developed T cells, we reconstituted thymectomized male or female recipient mice with bone marrow cells of mice transgenic for male H-Y antigen–specific T cell receptor (TCR). It was revealed that the T cells bearing self-antigen–specific TCR were not deleted in thymectomized male recipients. More importantly, the absence of H-Y antigen–specific T cells in thymectomized female recipients suggests positive selection of extrathymically developed T cells by the self-antigen. The extrathymically developed T cells in male mice expressed interleukin (IL)-2 receptor β chain (IL-2Rβ) and intermediate levels of CD3 (CD3int) but were natural killer cell (NK)1.1−. They rapidly produced interferon γ but not IL-4 after TCR cross-linking. Furthermore, a similar pattern of cytokine production was observed in CD3intIL-2Rβ+NK1.1− cells in normal mice which have been shown to develop extrathymically. These results suggest that extrathymically developed CD3intIL-2Rβ+NK1.1− cells in normal mice are also positively selected by self-antigens.
Abstract In order to study pregnancy‐induced changes in cell‐mediated immunity to Listeria monocytogenes , acquired resistance and T cell functions in pregnant mice were compared with those in nonpregnant mice after immunization with viable listerial cells. Impaired generation of acquired resistance was evident in pregnant mice from the impaired elimination of bacteria and poor survival after secondary challenge. Delayed footpad reactivity to listerial antigen was also lower in the pregnant mice. When immune spleen cells were examined for their ability to produce macrophage activating factor in vitro , culture supernatants from pregnant‐mouse spleen cells with listerial antigen showed far less ability to render macrophages cytostatic for P815 mastocytoma cells. To elucidate further the impairment of listeria‐immune T cell generation in pregnant mice, a local transfer experiment was carried out. When a given number of immune spleen cells was transferred locally into the footpads of naive mice, both delayed footpad reaction and local protection were much lower in the pregnant mice. This local transferability of the reactions was abrogated after treatment of cells with anti‐Thy 1 antibody plus complement. These findings indicate that pregnancy impairs the generation of specific T cells capable of contributing to acquired resistance to L. monocytogenes . Possible mechanisms for this impairment and the relationship to macrophage functions are discussed.
Murine delayed hypersensitivity (DTH) was induced by the cooperation of two subsets of T cells.One of these subsets (Tmd) produces the antigen-specific DTH augmentation factor (DAF).The other (Tm) receives DAF which is needed for the induction of DTH by antigen stimulation.These two types of T cells require the presence of the thymus only for a short term in their differentiation.In this paper, bone marrow cells were transferred to irradiated syngeneic mice and the rapid recovery of the functions of Tprod and Tm were investigated suggesting a low degree
Spleen cells of female C57BL/6 mice, preimmunized to male histocompatibility antigen, elicited splenomegaly in adult male recipients and caused mortality of the newborn recipients. These cells, upon stimulation in vitro with the male antigen, were cytotoxic to male target cells.
More than 60 mouse monoclonal antibodies directed to cytochrome c from Candida krusei with different specificities were raised. Most of these monoclonal antibodies, except for three of them, did not cross-react with bovine cytochrome c. By the immuno