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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunization of naive or specifically primed C3H/HEJ with irradiated B10.BR spleen cells via the hepatic portal vein leads to an antigen specific decrease in the proliferative and cytotoxic response to B10.BR antigen assayed in vitro (and to increased graft survival of B10.BR grafts in vivo). This effect seems to be mediated in the main by a decrease in IL-2 production from CD4+ T lymphocytes of mice given antigen by the portal route, which is in turn caused by a decreased precursor frequency of IL-2-producing cells. No clear decrease in IL-4 production was seen. Hepatic APC isolated from mice receiving antigen via the portal vein were unable to induce IL-2 production from a C3H/HEJ anti-B10.BR cell line in vitro, in contrast to splenic APC derived from the same mice. Even when antigen was given by conventional (systemic) intravenous routes (in this case via the lateral tail vein) hepatic APC isolated from those mice were unable to stimulate IL-2 production from this cell line. Furthermore, 24 h exposure of a cell line to antigen pulsed hepatic APC left those cells refractory to a subsequent restimulation with antigen presented by splenic APC. Spleen lymphoid cells from primed mice challenged in vivo with B10.BR liver cells (i.v.) were similarly unable to produce IL-2 on rechallenge in vitro with irradiated B10.BR spleen cells, though no defect was seen if in vivo challenge was with B10.BR spleen cells. These data imply that presentation of multiple minor cell surface antigens by hepatic APC leads to specific anergization of IL-2 producing T cells, in a fashion which seems to be distinct from that previously reported as due to 'veto-like' activity.
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PMID:Immunosuppression induced by hepatic portal venous immunization spares reactivity in IL-4 producing T lymphocytes. 142 92

Intravenous injection of semiallogeneic (C57BL/6XDBA/2)F1 lymphocytes into adult C57BL/6 recipient mice not only, as previously reported, reduces the recipients' cytotoxic T lymphocyte response in a subsequent in vitro mixed lymphocyte reaction against the injected cell type, but also reduces Th cell function in the same MLR. Thus lymphoid cells derived from the injected mice were greatly reduced in their ability to proliferate and to produce IL-2 in response to (C57BL/6XDBA/2)F1 stimulator cells in vitro, whereas third party responses were unaffected. This appears to be due to a reduction in the precursor frequency of IL-2-producing T lymphocytes specific for the injected cells as measured by limiting dilution analysis. Similar donor-specific reduction in the frequency of precursors of IL-2-producing cells was seen after i.v. injection of A.TL lymphocytes into A.TH recipients (differing at class II determinants I-A and I-E, but identical at K and D). Here there also appeared to be a functional clonal deletion of precursors of IL-2-producing Th cells, shown directly to be class II MHC reactive and CD4+. There is strong evidence that the reduction of class I-specific cytotoxic responses in the injected mice is a manifestation of donor cells that function as veto cells, i.e., that function as deletional APC that inactivate class I-reactive CTL precursors that recognize them. Our data in this study show that class II-specific Th responses are similarly reduced in the injected mice and suggest that CD4+ class II-reactive precursors of Th cells may be functionally inactivated in vivo by donor cells via a veto-like mechanism.
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PMID:In vivo functional clonal deletion of recipient CD4+ T helper precursor cells that can recognize class II MHC on injected donor lymphoid cells. 167 1

Allogeneic chimeras are valuable tools for studies of complex immune cell interactions in vivo. Mice with severe combined immune deficiency (scid) should be ideal hosts for chimerism with allogeneic bone marrow cells as these animals lack mature T and B lymphocytes capable of reacting against donor alloantigens. However, it has been difficult to achieve full reconstitution of adult scid mice even using coisogenic bone marrow grafts without prior irradiation of the recipient. We explored ways to generate complete reconstitution of scid mice with allogeneic bone marrow. Unirradiated adult scid recipients of allogeneic bone marrow were only marginally reconstituted. Adult scid mice pretreated with 250 R were reconstituted with allogeneic bone marrow as measured by serum IgM concentration, peripheral lymphoid cellularity, and mitogen responses, but a potentially important immunologic deficit was found in these mice: 250 R caused a 70% loss of scid macrophages and dendritic cells which persisted at least 5 months. By contrast, when scid mice were injected i.p. with allogeneic bone marrow within the first 24 h after birth, rapid and complete reconstitution of both T and B cell lineages was achieved, and the animals had APC that were both donor and host in origin. Considering the extent and duration of engraftment (43 wk) by allogeneic cells in neonatally transplanted scid mice, it was anticipated that their bone marrow would be chimeric. However, the bone marrow contained very few donor-derived cells, suggesting that lymphopoiesis may be taking place in other organs in these chimeras.
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PMID:Allogeneic chimerism in scid mice after neonatal transfer of bone marrow. 173 27

As an approach to defining the anatomic sites of T cell activation in situ, we have developed an immunocytochemical stain for IL-2, a T cell-derived cytokine synthesized shortly after Ag-induced activation. Analysis of lymph nodes from mice immunized with keyhole limpet hemocyanin emulsified in CFA demonstrates that the IL2+ cells appear in a perivascular location 4 days after antigenic challenge. After germinal centers develop, IL-2+ cells are situated in a parafollicular pattern. Serial sections stained for different types of APC, including B cells, interdigitating dendritic cells, and macrophages, demonstrate a close physical association between IL-2+ cells and macrophages. These findings may have important implications for defining how APC bearing processed Ag and Ag-specific T cells interact in the complex environment of lymphoid tissues.
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PMID:Histologic analysis of T lymphocyte activation in reactive lymph nodes. 188 Apr 15

The seminal observation made 30 years ago that T cells do not discriminate between native and denatured proteins, whereas B cells generally do, can now be explained by the fact that T cells never see antigens in their native conformation and that intact proteins cannot associate simultaneously with MHC molecules and the TCR. This difference in the ability to recognize antigen based on conformational specificity appears to be a consequence of the fact that the T cell sees antigen not free in solution, but on the surface of an APC in association with MHC molecules. The metabolic events that protein antigens undergo within APC, prior to their presentation in an appropriately processed form to T cells, are called antigen processing. The end-product of antigen processing for CD4+ T cells is a relatively short peptide fragment bound to class II MHC molecules on the surface of an APC that can be recognized by the TCR on the T cells. Because this event is difficult to monitor directly, antigen processing can only be assayed in conjunction with the temporally distal event of T-cell activation, manifested ultimately as proliferative responses or lymphokine secretion. In addition to occupancy of the TCR by the peptide/class II complex, several other antigen-nonspecific receptor-ligand interactions between APC and T cells are required for optimal T-cell activation. M phi, B cells, and LC/DC comprise the principal APC for CD4+ T cells. M phi and B cells have been studied extensively with respect to their antigen processing and presenting capacities. Only recently, however, have such capacities been investigated in LC and DC; these studies now indicate freshly isolated LC (but not cultured LC and DC) to possess efficient antigen processing capabilities. In this respect, LC have been proposed to represent evolving (or "maturing") forms of DC: Freshly isolated LC (which retain morphologic and functional properties of epidermal LC in situ) are the equivalent of tissue forms of DC, whereas cultured LC resemble lymphoid or circulating DC. Cultured LC and DC appear to be the sole effective APC for inducing primary T-cell responses in vitro. Possibly underlying this property is the ability of cultured LC and DC (but not M phi, B cells, or freshly isolated LC) to induce formation of T-cell clusters during the course of such responses. The capacity of accessory cells to function as APC varies depending upon the type of APC and T cells examined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antigen processing and presentation by epidermal Langerhans cells. Induction of immunity or unresponsiveness. 197 19

Spleen dendritic cells (DC) and epidermal Langerhans cells (LC) belong to the same family of dendritic leukocytes and are considered to be prototypes of lymphoid DC and nonlymphoid DC, respectively. These cells are active APC in vitro and play a key role in the induction of primary T cell dependent immune responses in vivo. Two functional states of LC have been characterized in vitro, freshly isolated LC and cultured LC (cLC). That cLC closely resemble spleen DC in phenotype and function, has led to the hypothesis that LC undergo maturation toward DC while in culture, an event that has been correlated with the emigration of LC from skin into lymphoid organs. To date, however, DC have been studied only after overnight culture. To better understand the relationship between LC and DC, we examined DC shortly after their isolation from spleen, and after 24 h of culture. Freshly isolated DC (fDC) express high levels of MHC molecules and low levels of Fc gamma RII and C3biR; fDC also uniformly express the Ag recognized by the mAb 33D1, NLDC-145, and J11d. After culture, DC display a marked increase in the expression of MHC molecules, and they are induced to express the low affinity receptor for IL-2. By contrast, the expression of Fc gamma RII and F4/80 decreases with culture. With respect to function, fDC can efficiently present keyhole limpet hemocyanin to Ag-specific T cells, whereas cultured DC exhibit a marked reduction in this capacity. Finally, both fDC and cultured DC are capable of endocytosing surface Ia molecules, but only fDC are able to deliver them into acidic compartments. Our data indicate that fDC from spleen resemble freshly isolated LC from epidermis and that both cells undergo parallel changes during culture. These results suggest that LC and DC possess analogous attributes in vivo and respond similarly to external influences.
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PMID:Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture. 221 64

The expression of MHC class II antigens on potential APC is a crucial step in T-lymphocyte activation and the initiation of an immune response. The studies which are presented here were initiated to characterize the critical APC present in physiologically normal, untreated rats. Such a cell should constitutively express these antigens at high density and therefore provide the apparatus necessary to provoke both primary and secondary immune responses at any time. DAC were found to fulfill these criteria. In the absence of specific surface markers of rat DAC, the results are based on the strict combination of morphological appearance and functional activity. However, the high expression of MHC class II antigens may be regarded as semispecific markers for DAC which are distributed at strategic positions in many lymphoid and nonlymphoid tissues (Hart & Fabre 1981, Steiniger et al. 1984). The relatively low number of these cells observed in tissue sections and in in vitro isolates (0.1% of all cells) may explain their high activity as APC. This would facilitate the presentation of antigen in vivo to a sufficient number of competent T lymphocytes. DAC differentiate from a bone marrow progenitor cell pool preferentially under the influence of spleen cell-derived activities. Although the exact lineage has not yet been determined it may be fair to speculate that DAC form a new cell lineage probably related to interdigitating cells but not to macrophages which differentiate from bone marrow-derived precursors under the influence of colony-stimulating activities. However, the cooperation between DAC plus macrophages may provide the stage for T-lymphocyte activation and T-T collaboration (Mitchison 1990). There are still many open questions concerning the general role of DAC in vivo and in vitro. To further characterize rat DAC, their tissue distribution, role in the immune response and possible influence on intrathymic lymphopoiesis, with respect to T-lymphocyte subpopulations and the selection of the T-lymphocyte antigen-receptor repertoire, a panel of DAC-specific monoclonal antibodies must be generated in the future. Such antibodies will also be useful to study the mechanism by which DAC activate T lymphocytes.
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PMID:Lymphoid dendritic accessory cells of the rat. 225 88

Monomeric human gamma-globulin (HGG), when injected into adult mice, induces a state of specific immunologic unresponsiveness to further challenge with immunogenic forms of HGG. In this report we have directly determined the role of the thymus in the induction of HGG tolerance and the proliferative responsiveness of T cells from normal and HGG-tolerant mice. Draining lymph node T cells were isolated from HGG-tolerized and -challenged mice, and tested for their proliferative response to HGG in vitro. T cells from untreated but challenged adult CBA/CaJ and A/J mice proliferate in response to HGG, whereas such mice given monomeric HGG before challenge fail to show an HGG-specific proliferative response. APC from tolerant or nontolerant mice were equally effective in the support of Ag-specific proliferation of primed T cells. The influence of the thymus gland on HGG-induced T cell unresponsiveness was assessed by determining whether thymectomized mice could be tolerized to HGG. The results suggest that the generation of T cell tolerance to HGG is independent of thymic function as assayed by both antibody production in vivo and T cell proliferation in vitro. Unresponsiveness of T cells from tolerant mice was not a result of the presence of CD8+ cells since removal of CD8+ cells from lymph node T cells did not alter unresponsiveness to HGG in vitro. Further, mixing tolerant T cells with normal HGG-primed T lymphocytes did not inhibit proliferation of the HGG-primed cells. The results of this investigation suggest that this mouse model of tolerance to HGG represents a thymus-independent unresponsiveness of mature peripheral T cells to a nonself-Ag. Understanding the regulation of tolerance to HGG may give additional insight into the mechanisms required for the maintenance and possibly the induction of tolerance to certain self-Ag in peripheral lymphoid organs.
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PMID:The induction of peripheral T cell unresponsiveness in adult mice by monomeric human gamma-globulin. 247 97

The present study investigates the effects of i.v. presensitization with class II H-2-disparate allogeneic cells on various L3T4+ T cell functions including the capability of rejecting the corresponding allogeneic skin graft. C57BL/6 (B6) mice were i.v. presensitized with class II H-2 disparate B6-C-H-2bm12 (bm12) spleen cells. Such presensitization did not affect the bm12-specific L3T4+ T cell-mediated proliferative and interleukin 2 (IL-2)-producing capacities. A single cell suspension of (B6 x bm12)F1 spleen cells was depleted of APC by two round-passages over Sephadex G-10 columns. This APC-depleted fraction of (B6 x bm12)F1 cells failed to stimulate B6 responding cells in mixed lymphocyte reactions (MLR). The addition of recombinant IL-1 to the MLR restored anti-bm12 MLR responses, indicating that APC-depleted (B6 x bm12)F1 cells bear bm12 alloantigens but are unable to stimulate B6 anti-bm12 L3T4+ T cells. A single i.v. administration of APC-depleted (B6 x bm12)F1 cells into B6 mice resulted in almost complete abrogation of the capacity of recipient B6 lymphoid cells to give anti-bm12 MLR and IL2 production. This suppression was bm12 alloantigen-specific and attributed to the elimination or functional impairment of anti-bm12 T cell clones rather than the induction of suppressor cells. The tolerance was also observed in graft-rejection responses. The strikingly prolonged survival of bm12 skin grafts was produced when grafts were implanted into B6 mice which had been presensitized with APC-depleted, but not with untreated (B6 x bm12)F1 spleen cells. These results indicate that allo-class II H-2 antigen-reactive L3T4+ T cells are rendered tolerant by i.v. presensitization with APC-depleted fraction of the corresponding allogeneic cells.
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PMID:Tolerance induction of allo-class II H-2 antigen-reactive L3T4+ helper T cells and prolonged survival of the corresponding class II H-2-disparate skin graft. 252 64

Four BALB/c T cell clones from among a set propagated in the presence of concanavalin A (Con A) were selected on the basis of their ability to produce supernatant factors promoting high IgA plaque-forming cell (PFC) responses by 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin (TNP-KLH)-primed splenic B cells in the presence of TNP-SRBC. Such clones could be derived from cultures containing T cells not only from gut-associated lymphoid tissue, but also from the spleen. The selected clones all proliferated well in the presence of syngeneic, irradiated APC without either Con A or exogenous IL-2, but required both APC and Con A to produce helper factors. Factors from three of the clones helped B cells both to proliferate and to differentiate into IgM, IgG and IgA PFC. Factors from the fourth clone helped B cells differentiate into IgA and IgG PFC and may have promoted switching to these isotypes but did not support either B cell proliferation or generation of IgM PFC. Cross-linking of B cell receptors for antigen was not required for the response to the helper factors since TNP-SRBC were unnecessary and high concentrations of them were actually inhibitory.
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PMID:Con A-propagated, auto-reactive T cell clones that secrete factors promoting high IgA responses. 296 57


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