T cell-dependent suppression of antibody production. I. Characteristics of suppressor T cells following tolerance induction (original) (raw)
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T cell independent induction of antigen specific suppression of the antibody response
La Ricerca in clinica e in laboratorio
Immune spleen cells (from mice given 2 x 10(7) HRBC 14 days earlier) when mixed in vitro with carrier-primed syngeneic spleen cells (from mice given 2 x 10(5) HRBC 3 days earlier) are able to suppress the anti-TNP and anti-HRBC PFC response to TNP-HRBC. If immune thymocytes are substituted for spleen cells suppression is not observed. This suppression is antigen specific, resistant to anti-T treatment or x-irradiation, and is exerted by nylon wool-retained cells of the immune spleen cell population. An antigen specific suppressive factor is released from immune spleen cells in culture. Under these experimental conditions, suppression appears to be mediated by a specific product of B rather than T cells present in the immune spleen cell population.
In vitro induction of immunological tolerance
Cellular Immunology, 1989
IL-2 was previously shown to induce cytotoxic effecters with a broad spectrum of target specificities in thymus and spleen cell cultures. This study was designed to show whether T cells activated by H-2 allogeneic cells in MLC or by syngeneic tumor cells in MLTC are also potential targets for these cytotoxic effecters. We found that thymocytes activated in vitro for 5 days by rIL-2 were capable of killing tumor cells as well as activated T cells. Thymocytes activated by IL-2 were accordingly utilized as a means of effecting clonal deletion of T cells activated by H-2 allogeneic target cells in MLC. To establish whether the unresponsiveness is specific, IL-2-a&vated thymocytes were added as third party cells to MLC and MLTC. The results showed that both T cells, proliferating in response to H-2 allogeneic cells, and CTL, reactive against syngeneic tumors or H-2 allogeneic cells, are eliminated from the T cell pool. Only alloreactive T cells are specifically eliminated in MLC by IL-2-activated thymocytes, as the remaining T cells are capable of proliferating and generating CTL in response to antigenically unrelated third party allogeneic cells. The possibility that unresponsiveness might be due to soluble factors was ruled out by studies performed with a diffusable "chamber insert" culture system. The results provide evidence that IL-2-activated thymocytes induce in vitro T cell tolerance. o
Central tolerance induction in natural immunoglobulin-allotype-specific T cells
European Journal of Immunology, 2000
While self toleance is induced to IgG b 2a in Igh b/b mice, an anti-IgG b 2a T cell activity emerges in their Igh a/a congenic counterparts. This activity is revealed by postnatal transfer of Igh a/a T splenocytes into Igh a/b F 1 , in which total suppression of IgG 2a b expression is established. Here, we sought to determine whether the natural T cell unresponsiveness to IgG 2a b in Igh b/b mice involved a central tolerance. Based on the kinetics of postnatal thymic C + 2a b gene expression in Igh b/b mice, we transplanted thymi from Igh b/b donors of diverse ages into tolerogen-free Igh a/a nu/nu recipients. The state of T cell tolerance or responsiveness to IgG 2a b in these reconstituted nu/nu hosts was determined by monitoring the capacity of their splenocytes to induce suppression in Igh a/b F 1. These experiments demonstrated that: (i) in the Igh a/a nu/nu recipients of adult Igh b/b thymi, 33 to 65 % T splenocytes were from nu/nu recipient origin, but these peripheral Igh a/a T cells were rendered tolerant to IgG 2a b during their differentiation through the adult Igh b/b thymi, (ii) circulating IgG 2a b was not a prerequisite for this tolerance induction, (iii) Igh b/b thymic epithelium was unable to induce tolerance to IgG 2a b and (iv) IgG 2a b-producing/presenting cells, colonizing the Igh b/b thymi, were certainly responsible of full tolerance induction to IgG 2a b .
Induction of tolerance in peripheral T cells with monoclonal antibodies
European Journal of Immunology, 1990
Our goal has been to develop ways to tolerize the mature immune system to any defined antigen. In this report we show that peripheral (post-thymic) Tcells of mice can become tolerant to a range of antigens (human and rat immunoglobulins, and bone marrow and skin grafts that differ at multiple minor transplantation antigens). In the case of human gamma globulin (HGG), this required that the antigen be given under the cover of a short iourse of non-depleting anti-CD4 antibody, while for tolerance to skin and marrow grafts anti-CD8 antibody was also required. Tolerance to HGG could be reinforced by repeated injections of HGG, but was lost in the absence of any further exposure to antigen.This reversal of tolerance with time was due to new Tcells being exported from the thymus, as it was not observed in tolerized, adult thymectomized mice. In contrast, tolerance to marrow and skin grafts was permanent, presumably because the established grafts acted as a continuous source of antigen to reinforce the tolerant state. Tolerance could not be broken by the infusion of unprimed spleen cells and in one example (tolerance to Mls-la) there was clear evidence that specific peripheral T cells were anergic. We propose that anergic cells may themselves participate in reinforcing the tolerant state by competing at sites of antigen presentation.
Suppression of IgE antibody production in SJL mice
Cellular Immunology, 1983
Anti-DNP IgE antibody production was low and transient in SJL mice which were immunized with I qg DNP-Nb and 1 mg AI(O The immunized SJL mice were irradiated (60-540 R) 1 day after challenge. A dose higher than 180 R induced enhancement of anti-DNP IgE antibody production as compared to nonirradiated control mice, suggesting the existence of irradiationsensitive suppressor cells. Anti-DNP IgE antibody production was suppressed when immunized and irradiated SJL mice were injected with spleen cells from adult-thymectomized SJL mice. The donors of the spleen cells were thymectomized 2 or 4 months previously, and this suggests that the suppressor cells from unprimed mice are long-living T cells.
European Journal of Immunology, 1977
A previous study of primary and secondary immune responses of rats and mice immunized against various protein antigens allowed us t o describe a population of immunocytes containing, synthesizing and secreting immunoglobulins without detectable antibody function against the antigen injected (IFC). We here report their T cell-dependence. Mice, thymectomized, irradiated and reconstituted with bone marrow or fetal liver cells, generally show neither ant ibody-forming cells (AFC) nor cells synthesizing immunoglobulin without detectable antibody function. In some mice, probably only partly T cell-deprived, antibody-containing cells were seen, and at that time they were associated with cells synthesizing immunoglobulin without detectable antibody function. For most of the animals studied in primary response, however, the IFC population remained higher than the AFC population throughout the immune response. In normal animals immunoglobulin-synthesizing cells were predominant a t the beginning of the immune response, then decreased and progressively replaced by antibody-synthesizing cells. After the first injection or after two stimuli, the number of responders among T celldeprived mice increased progressively. Finally, these experiments indicate that both cells synthesizing immunoglobulins without detectable antibody function and specific AFC are thymus-dependent and rule o u t the hypothesis according t o which horseradish peroxidase is a polyclonal B cell activator.
Induction of tolerance to an IgG autoantibody
Proceedings of the …, 1992
Nonautoimmune mice transgenic for the heavy chain of an IgG2b anti-double-stranded-DNA antibody express the transgene in lymphoid organs and display partial allelic exclusion of this y2b transgene. The spleens ofthese mice are characterized by marked B-cell depletion. Although there are B cells in these mice that express the transgene and recognize double-stranded DNA, they are anergic in vivo. Recovery from the state of anergy occurs in vitro after lipopolysaccharide stimulation. Thus this transgenic model demonstrates the induction ofselftolerance to an IgG autoantibody.