Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon γ–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.
Taking advantage of recent findings about membrane fluidity, we have studied and compared the biosynthetic capacities of fetal or neonatal mouse B (bone-marrow derived) lymphocytes (until 10 days after birth) and adult B lymphocytes. Although both early and adult lymphocytes can synthesize surface immunoglobulins, they have a different physiological behavior after interaction with a ligand (antiimmunoglobulin sera or antigen), either in vivo or in vitro. Fetal and neonatal lymphocytes bearing surface immunoglobulins do not reexpress their membrane receptors after capping and endocytosis promoted by anti-immunoglobulin sera. On the other hand, adult lymphocytes resynthesize completely their receptors after the same treatment. Furthermore, intrafetal injections of hemocyanin in pregnant mice lead to a striking decrease in the number of hemocyanin-binding cells. It seems plausible that this non-reexpression of surface immunoglobulins could be the first step in tolerance establishment. The mechanisms by which the immunological repertoire is developed are still largely unknown. Useful information may be obtained from studies of lymphocyte differentiation. In some species, for example, the mouse, immunological maturity is attained only after birth (1). Several studies, however, indicate that immunoglobulin receptors appear on the membrane of some lymphoid cells before the animal is able to synthesize antibody in response to antigenic stimulation (2-4). The following experiments were designed to investigate the rate of appearance of B (bone-marrow-derived) lymphocytes and the physiological effects of treating early B lymphocytes with anti-immunoglobulin sera or early fetal antigen-binding cells with antigen. The main conclusions drawn from this study are that B lymphocytes and keyhole limpet hemocyanin-(KLH) binding cells can be detected early in fetal liver and spleen and that, until approximately 10 days after birth, the interaction of lymphocytes with anti-immunoglobulin sera or with antigen leads to the inactivation (no receptor reexpression) of the lymphocytes that bind the ligand. No such inactivation occurs after that period. Furthermore, intrafetal injections of KLH at 15 days' gestation lead to a marked decrease in the number of KLH-binding cells. MATERIALS AND METHODSAntisera and Membrane Immunofluorescence. Spleen and liver were removed from fetuses of timed pregnant BALB/c mice at different days of gestation, and from newborn mice.Cell suspensions were made and processed for membrane immunofluorescence using fluorescein-(Fl-) or rhodamine-(Rho-) labeled, polyspecific anti-Ig, whose properties have been described in detail previously (5). The results were unaffected by adsorption of these antisera with adult liver and kidney cells. Furthermore, when adult spleen cells are first treated, in capping conditions, with tobacco mosaic virus (TMV) and Rholabeled anti-TMV and then, in non-capping conditions, with Fl-labeled anti-Ig, TMV-binding cells with coincident fluorescence can be detected (5). Thus, c...
In this paper, we have considered the problem of selection of available repertoires. With Ab2 as immunogens, we have used the idiotypic cascade to explore potential repertoires. Our results suggest that potential idiotypic repertoires are more or less the same within a species or between different species. A given idiotype "à la Oudin" can become a recurrent one within the same outbred species or within different species. Similarly, an intrastrain crossreactive idiotype can be induced in other strains, even though there is a genetic disparity between these strains. The structural basis of this phenomenon has been explored. We next examined results showing the loss and gain of recurrent idiotypes without any intentional idiotypic manipulation. A recurrent idiotype can be lost in a syngeneic transfer and a private one can become recurrent by changing the genetic background. The change of available idiotypic repertoires at the B cell level has profound influences on the idiotypic repertoires of suppressor T cells. All these results imply that idiotypic games are played by the immune system itself, a strong suggestion that the immune system is a functional idiotypic network.
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