scholarly journals Dendritic Cells: Cellular Mediators for Immunological Tolerance

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chun Yuen J. Chung ◽  
Dirk Ysebaert ◽  
Zwi N. Berneman ◽  
Nathalie Cools
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Inflammatory Diseases ◽  
Immunological Tolerance ◽  
Immunosuppressive Drugs ◽  
Peripheral Tolerance ◽  
Regulatory Function ◽  
Clonal Deletion

In general, immunological tolerance is acquired upon treatment with non-specific immunosuppressive drugs. This indiscriminate immunosuppression of the patient often causes serious side-effects, such as opportunistic infectious diseases. Therefore, the need for antigen-specific modulation of pathogenic immune responses is of crucial importance in the treatment of inflammatory diseases. In this perspective, dendritic cells (DCs) can have an important immune-regulatory function, besides their notorious antigen-presenting capacity. DCs appear to be essential for both central and peripheral tolerance. In the thymus, DCs are involved in clonal deletion of autoreactive immature T cells by presenting self-antigens. Additionally, tolerance is achieved by their interactions with T cells in the periphery and subsequent induction of T cell anergy, T cell deletion, and induction of regulatory T cells (Treg). Various studies have described, modulation of DC characteristics with the purpose to induce antigen-specific tolerance in autoimmune diseases, graft-versus-host-disease (GVHD), and transplantations. Promising results in animal models have prompted researchers to initiate first-in-men clinical trials. The purpose of current review is to provide an overview of the role of DCs in the immunopathogenesis of autoimmunity, as well as recent concepts of dendritic cell-based therapeutic opportunities in autoimmune diseases.

scholarly journals Mechanisms of the induction of autoimmunity

2005 ◽  
Vol 133 (Suppl. 1) ◽  
pp. 9-15 ◽  
Author(s):  
Marija Mostarica-Stojkovic
Keyword(s):  
Immune System ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Molecular Mimicry ◽  
The Body ◽  
Peripheral Tolerance ◽  
High Avidity ◽  
Main Function ◽  
Clonal Deletion ◽  
Genetic Traits

The main function of the immune system is to protect the body by responding to invading microorganisms. Immunologic tolerance is the basic property of the immune system that provides for self/non-self discrimination so that the immune system can protect the host from external pathogens without reacting against itself. Central tolerance is achieved by the clonal deletion of self-reactive lymphocytes expressing receptors with high avidity for self. Autoreactive lymphocytes which escaped selection in the central lymphoid organs are present in the peripheral repertoire but but are kept under control by multiple diverse peripheral tolerance mechanisms acting either directly on the self-reactive T cell (T-cell intrinsic) or indirectly via additional cells (T-cell extrinsic). Intrinsic mec hanisms include ignorance of autoantigens, anergy, phenotype skewing or activation-induced cell death of autoreactive T lymphocytes, while extrinsic mechanisms act through immature and/ or tolerogenic dendritic cells as well as different types of regulatory cells. Autoimmune diseases are associated with humoral or cell-mediated immune reactions against one or more of the body?s own constituents. Activation and clonal expansion of autoreactive lymhocytes is a crucial step in the pathogenesis of autoimmune diseases. They result from the complex interactions between genetic traits and environmental factors, among which infections are the most likely cause. Several basic mechanisms may be operating whereby an infectious agent actually induces apparent autoimmne reactivity including molecular mimicry, bystander activation, induction of costimulation, polyclonal activation, altered processing and expression of cryptic antigens. Although many questions regarding autotolerance and etiop athogenestis of autoimmunity have yet to be resolved, it is evident that multiple overlapping pathways are operative in establishing, maintaining and breaking autotolerance, as well as during the initiation, progression, and final effector phases of autoimmunity.

Resting B Cells Suppress CD8+ T Cell Function and Prevent the Induction of Graft Versus Host Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3111-3111
Author(s):  
David S. Ritchie ◽  
Victoria Watt
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
Graft Versus Host Disease ◽  
Cd8 T Cell ◽  
Regulatory Function ◽  
In Vivo Models ◽  
Host Disease ◽  
Graft Versus Host

Abstract B cells have been variously shown to induce direct tolerance of antigen specific CD8+ T cells, induce T cell anergy via TGF-b production, down regulate IL-12 production by dendritic cells (DC) and influence Th1/Th2 differentiation via the production of regulatory cytokines. Through these mechanisms, B cells can exert a regulatory function in in vivo models of T cell immunity including, experimental autoimmune encephalitis (EAE) and rheumatoid arthritis (RA). Recently, B cells have been shown to be essential in the prevention of effector T cell differentiation in a model of autoimmunity. We have previously shown that resting B cells inhibited tumor protection induced by dendritic cells vaccination. Inhibition of DC immunity by B cells was independent of presentation of major histocompatibility molecule (MHC) class-I bound tumor antigen but dependent on the expression of class-II MHC. Furthermore the inhibitory effect of B cells was lost if the B cells were activated by CD40L or if CD4+/CD25+ regulatory T cells (Treg) were depleted. These studies have been further extended to examine the role of resting B cells on the induction and severity of graft versus host disease (GVHD) induced in a major MHC mismatch model. We have found that mice transplanted with B cell depleted marrow revealed more rapid CD8+ T cell engraftment, higher IL-2 and IFN-γ production, more severe GVHD and shorter survival. Conversely, those who received additional resting B cells at the time of marrow infusion were substantially protected from GVHD. These findings indicate that resting B cells may regulate T cell activation, in part via the suppressive effects of Treg, but also through their important role in T cell homeostasis. Resting B cells may therefore limit the efficacy of DC based immunotherapy or alternatively be used therapeutically to limit CD8+ T cell autoimmunity including GVHD.

Double Negative T Cells Influence TCR VB Variablity to Induce Allotolerance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 759-759
Author(s):  
Zachariah A. McIver ◽  
Marcin Wlodarski ◽  
Jennifer Powers ◽  
Christine O’Keefe ◽  
Tao Jin ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Peripheral Tolerance ◽  
Double Negative ◽  
Clonal Deletion ◽  
Tcr Repertoire ◽  
Double Negative T Cells

Abstract Immune alloresponsiveness following allogeneic HSCT is influenced by the dynamics of immune reconstitution and development of allotolerance. In general, tolerance is induced by thymic clonal deletion (central) and apoptosis or suppression of alloresponsive lymphocytes by regulatory T cells in the periphery. We have recently demonstrated that the size of the TCR repertoire within the CD4 and CD8 compartments can be assessed using VB spectrum by flow cytometry, and expansions/losses of individual TCR VB families can be used as a surrogate marker of TCR variability. (Exp. Hem.32: 1010–1022; Br. J. Haematol.129:411–419). Additionally, regulatory T cells can also impact the clonal contractions and expansions within the TCR VB repertoire. Various types of regulatory T cells have been described including CD4+CD25+, CD8+, NK T−cells, and CD3+CD4/CD8− double negative T cells (DN Tregs). In our current study we investigated the role of DN Tregs on the restoration of immune repertoire diversity. We hypothesized that alloresponsiveness clinically detected as a manifestation of GvHD may be associated with oligoclonal T−cell expansions, and in this context decreased numbers of regulatory T cells suggest deficient tolerizing function by regulatory T cells including DN Tregs. Here we studied a cohort of 60 HSCT recipients (AML, CML, CLL, NHL, AA, and PV), of which 25 patients received matched unrelated donor grafts and 35 received matched sibling donor grafts. Blood was sampled between 2003–2006 at monthly intervals after HSCT, and flow cytometry for TCR repertoire in CD4 and CD8 cells as well as the numbers of DN cells were recorded. Additionally, separate samples were collected for measurement of chimerism and were included in analysis when donor lymphoid chimerism was > 60%. A subset analysis was performed based on the presence/absence of GvHD. For the 27/60 (45%) patients with episodes of GvHD, results were obtained at the time of diagnosis of GvHD (grade > 2), while for patients in whom notable GvHD was not captured, the steady−state values at corresponding times were used for analysis. For all patients serial evaluations were available. For the purpose of this study, significant VB expansions/contractions were defined as +/− 2 standard deviation over the average VB family size. Using Cox proportional hazards analysis to identify univariate risk factors for GVHD, CD8 VB TCR contractions > 14 VB families (58.3% contraction of entire CD4 VB repertoire) constituted a strong indicator for increased risk (HR=7.61, p=0.011). This observation is consistent with the fact that oligoclonality of alloreactive T cell clones is frequently accompanied by a significant contraction/loss of remaining VB families and may herald heightened alloresponsiveness as a manifestation of GvHD. Estimation for correlation by Pearson’s correlation coefficient also demonstrated that percentage of DN cells strongly correlated with a normalization of CD4 VB TCR repertoire (lower number of expansions; N=57, R= −0.51, p=0.027), supporting our hypothesis that DN cells participate in peripheral tolerance and suppress proliferative, alloresponsive CD4 clones. In summary, our results further characterize TCR variability post HSCT and define the role of DN cells in the induction of allotolerance.

scholarly journals Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3632-3638 ◽  
Author(s):  
Elena Gonzalez-Rey ◽  
Alejo Chorny ◽  
Amelia Fernandez-Martin ◽  
Doina Ganea ◽  
Mario Delgado
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Vasoactive Intestinal Peptide ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Blood Monocytes ◽  
Endogenous Factors ◽  
Tolerogenic Dcs

Induction of antigen-specific tolerance is critical for autoimmunity prevention and immune tolerance maintenance. In addition to their classical role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T (Treg) cells. The possibility of generating tolerogenic DCs opens new therapeutic perspectives in autoimmune/inflammatory diseases. Characterizing endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. We here report that the immunosuppressive neuropeptide vasoactive intestinal peptide (VIP) induces the generation of human tolerogenic DCs with the capacity to generate CD4 and CD8 Treg cells from their respective naive subsets. The presence of VIP during the early stages of DC differentiation from blood monocytes generates a population of IL-10-producing DCs unable to fully mature after the effects of inflammatory stimuli. CD4 Treg cells generated with VIP-differentiated DCs resemble the previously described Tr1 cells in terms of phenotype and cytokine profile. CD8 Treg cells generated with tolerogenic VIP DCs have increased numbers of IL-10-producing CD8+CD28--CTLA4+ T cells. CD4 and CD8 Treg cells primarily suppress antigen-specific TH1-mediated responses. Therefore, the possibility of generating or expanding ex vivo tolerogenic DCVIPs opens new therapeutic perspectives for treating autoimmune diseases and graft-versus-host disease after allogeneic transplantation in humans.

Ex vivo–expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts

Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2640-2648 ◽  
Author(s):  
Tomoyoshi Yamano ◽  
Sho Watanabe ◽  
Hiroyuki Hasegawa ◽  
Toshihiro Suzuki ◽  
Ryo Abe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Peripheral Tolerance ◽  
Skin Grafts ◽  
Major Histocompatibility ◽  
Clonal Deletion ◽  
Activated T Cells ◽  
Donor Skin ◽  
Major Histocompatibility Complexes

Abstract Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide–major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive thymocytes. For peripheral tolerance, injection of FLDCs induced donor-specific T-cell unresponsiveness and prolonged survival of donor-derived skin grafts. Tolerance induction by adoptive transfer of FLDCs could be a useful approach for promoting graft acceptance after organ transplantation.

scholarly journals Dendritic cells transduced with TIPE-2 recombinant adenovirus induces T cells suppression

2020 ◽  
Author(s):  
Shudong Liu ◽  
jie wang ◽  
Wenyan Li ◽  
Hui Shi ◽  
Changlong Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Suppression ◽  
Cytokine Production ◽  
Recombinant Adenovirus ◽  
Inflammatory Diseases ◽  
Cd8 T Cell ◽  
Negative Regulator ◽  
Activation Marker

Abstract Introduction: TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the role of immune suppression of dendritic cells (DCs) transduced with TIPE-2 has not been well studied. Methods: In this study, DCs were transduced with TIPE-2 recombinant adenovirus, and then were cocultured with allogeneic CD4+ or CD8+T cells. The proliferation, cytokine production and activation marker levels of CD4+ or CD8+T cell were detected. Results: The data demonstrated that T cell proliferation, cytokine production and activation marker levels were attenuated after treated with TIPE-2 transduced DCs. Conclusions: These results suggested that TIPE-2 transduced DCs are capable of inducing allogeneic CD4+ or CD8+T cell immune suppression, which provide a promising way for the therapeutical strategies of transplantation or autoimmune diseases.

Increased Expression of CD152 by Normal T Lymphocytes in Untreated Patients with B Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 963-963
Author(s):  
Marina Motta ◽  
Bobby Shelvin ◽  
Susan Lerner ◽  
Michael Keating ◽  
William G. Wierda
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Lymphocytic Leukemia ◽  
Peripheral Tolerance ◽  
Regulatory Function ◽  
Cell Phenotype ◽  
Costimulatory Receptor

Abstract Patient with chronic lymphocytic leukemia (CLL) have defects in both cellular and humoral immunity. Despite reported increases in absolute T cell counts in untreated patients with CLL, abnormalities of T cell phenotype and function have been described as well as progressive hypogammaglobulinemia. Furthermore, defects are compounded by current treatments for the disease. Expansion and differentiation of normal antigen-specific T cells depends upon two signals: binding of the T cell receptor to antigen presented in the context of self MHC molecules and ligation of a costimulatory receptor. CD28 is the primary T cell surface costimulatory receptor and is constitutively expressed on almost all CD4+ and about 50% of CD8+ T cells. The ligands CD80 and CD86 bind CD28, thereby transducing the second enhancing signal for T cell proliferation and cytokine secretion. CD152 (CTLA-4) has homology to CD28 and binds to CD80 and CD86 with much higher affinity, but plays a critical role in the down regulating T cell responses and maintenance of peripheral tolerance. Surface CD152 is not normally expressed on resting T cells, but is induced upon activation. We hypothesized that in previously untreated patients with CLL, T cell anergy is the result of increased expression of CD152. Therefore, we studied the expression of surface and cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells from blood (N=40) and bone marrow (N=14) of previously untreated patients with CLL. Also, the activation status of these T cells was evaluated by evaluating IL-2 receptor subunit expression. CD4+ and CD8+ T cells from patients with CLL demonstrated significant increase in sCD152 and cCD152 compared to T cells from normal donors (Table 1). Table 1 Expression of CD152 by T Cells Mean % Positive T Cell Population Normal CLL P-value sCD152 N=13 N=40 CD4+ 0.8 5.0 <.01 CD4+/CD25+ 1.8 11.5 <.05 CD8+ 1.8 5.0 <.05 cCD152 N=13 N=19 CD4+ 6.9 40.4 <.01 CD4+/CD25+ 26.6 48.0 <.01 CD8+ 1.3 16.9 <.05 Furthermore, patients with CLL had an increased proportion of CD4+/CD25+/CD152+ cells. This subpopulation of T cells is known to have a regulatory function. T cells from patients with CLL (N=25) also showed an activated immunophenotype with significantly increased proportion of CD4+ and CD8+ T cells co-expressing the CD122/CD25 subunits of the IL-2 receptor compared to normal donors (N=10). No significant differences were seen in proportion or pattern of expression of these antigens between peripheral blood and bone marrow cells. These findings suggest that the T cells have been activated, however, may be primed for hyporesponsiveness and peripheral tolerance by expression of CD152. Correlations between CD152 expression and relevant clinical and biological variables were made in these previously untreated patients. The number of CD4+/CD152+ and CD4+/CD25+/CD152+ cells from patients with CLL inversely correlated with serum IgG and IgA levels. These findings suggest a further possible involvement of CD152 in the possible suppression of normal B cells in patients with CLL. The proportion of CD4+/CD25+/CD152+ cells also correlated with advanced Rai stage. In summary, T cells from patients with CLL are potentially primed for anergy by expression of CD152. Functional studies to investigate the role of CD152 and CD4+/CD25+/CD152+ cells in patients with CLL are ongoing, with the goal to develop immunotherapeutic strategies.

Immunosuppressive Drugs up-Regulate the Immunoinhibitory Receptor Osteoactivin On Human Monocyte-Derived Dendritic Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3284-3284
Author(s):  
Sabine Braun ◽  
Michael Gutknecht ◽  
Mark-Alexander Schwarzbich ◽  
Lothar Kanz ◽  
Helmut R Salih ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cyclosporine A ◽  
Cell Activation ◽  
Immunosuppressive Drugs ◽  
Type I ◽  
Transmembrane Glycoprotein ◽  
The Impact

Abstract Abstract 3284 Introduction: Dendritic cells (DC) abundantly express the type I transmembrane glycoprotein Osteoactivin (OA) - also known as transmembrane glycoprotein NMB and DC-HIL - compared to low expression levels on monocytes. Antigen-presenting cells interact via OA with the type I transmembrane proteoglycan syndecan-4 (SD-4) on T cells which inhibits T cell activation. We previously reported on increased expression of OA upon exposure of monocyte-derived DC (moDC) to immunosuppressive drugs (e.g., Gutknecht et al ASH annual meeting 2011). Here we extended these analyses and comparatively analyzed the impact of various immunsuppressive drugs (ID) on moDC phenotype and function. Methods: The moDC were generated from blood monocytes by plastic adherence and exposure to GM-CSF and IL-4. Clinically relevant concentrations of ID were added to the culture medium every second day starting with the first day of culture (cyclosporine A: 1μg/ml, prednisolone: 3.5μg/ml, tacrolimus: 10ng/ml, mycophenolat-mofetil 0.1μM, methotrexat 230ng/ml). Cells were harvested for immunophenotyping by flow cytometry, western-blotting and real-time PCR. Cytokine release by moDC was determined on day 7 by ELISA. Functional properties were determined by mixed lymphocyte reactions (MLR) on day 7 of culture. Results: Exposure of moDC to therapeutic concentrations of prednisolone resulted in significantly reduced expression of the costimulatory molecules CD83 and CD86 and increased levels of the monocyte marker CD14, indicative of impaired differentiation. Tacrolimus significantly increased CD14 expression and reduced CD83 expression, while the other ID did not cause significant alterations. All ID altered the release of the immunomodulatory cytokines IL-10, IL-6 and TGF-ß. Notably, all ID except cyclosporine A caused a substantial upregulation of the immunoinhibitory receptor OA in moDC. The extent of OA expression increased over time of exposure to ID during differentiation and resulted in reduced capacity of the moDC to stimulate allogenic T cells which could be restored by disruption of OA/SD-4 interaction using a blocking OA antibody. Conclusion: Increased expression of OA on moDC upon exposure to ID contributes to inhibition of T-cell activation. The mechanisms underlying the differential effect of cyclosporine A are presently under study. Our results indicate that targeting OA/SD-4 interaction may hold promise for modulation of T cell responses in various pathophysiological conditions and immunotherapeutic strategies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo

2001 ◽  
Vol 194 (6) ◽  
pp. 769-780 ◽  
Author(s):  
Daniel Hawiger ◽  
Kayo Inaba ◽  
Yair Dorsett ◽  
Ming Guo ◽  
Karsten Mahnke ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Steady State ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interferon Γ ◽  
Peripheral Tolerance ◽  
Antigen Delivery

Dendritic cells (DCs) have the capacity to initiate immune responses, but it has been postulated that they may also be involved in inducing peripheral tolerance. To examine the function of DCs in the steady state we devised an antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted endocytic receptor, DEC-205. Our experiments show that this route of antigen delivery to DCs is several orders of magnitude more efficient than free peptide in complete Freund's adjuvant (CFA) in inducing T cell activation and cell division. However, T cells activated by antigen delivered to DCs are not polarized to produce T helper type 1 cytokine interferon γ and the activation response is not sustained. Within 7 d the number of antigen-specific T cells is severely reduced, and the residual T cells become unresponsive to systemic challenge with antigen in CFA. Coinjection of the DC-targeted antigen and anti-CD40 agonistic antibody changes the outcome from tolerance to prolonged T cell activation and immunity. We conclude that in the absence of additional stimuli DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness.

scholarly journals Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus.

1991 ◽  
Vol 173 (3) ◽  
pp. 539-547 ◽  
Author(s):  
O Mazda ◽  
Y Watanabe ◽  
J Gyotoku ◽  
Y Katsura
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Development ◽  
Cell Receptor ◽  
Cell Development ◽  
Clonal Deletion ◽  
Fetal Thymus ◽  
Effector Cells

The present study was performed to identify cells responsible for the elimination of T cells reactive with minor lymphocyte-stimulating (Mls) antigens during T cell development. Experiments were carried out in a fetal thymus organ culture (FTOC) system. To examine the tolerance-inducing activity, various populations of cells from adult CBA/J (Mls-1a) mice were injected into deoxyguanosine (dGuo)-treated FTOC of C3H/He (Mls-1b) mice with a microinjector, and 2 d later, the thymus lobes were injected with fetal thymus cells from C3H/He mice as T cell precursors. After 14 d of cultivation, cells were harvested and assayed for the expression of the T cell receptor V beta 6 element. The absence or marked reduction of T cells expressing V beta 6 at high levels (V beta 6high) was regarded as indicating the deletion of Mls-1a-reactive T cells. T cell-depleted populations of thymic as well as splenic cells from CBA/J mice were able to induce clonal deletion. Further characterization of the effector cells was carried out by fractionating the spleen cells before injecting them into dGuo-FTOC. None of the dish-adherent population, dish-nonadherent population, or purified B cells alone were able to induce clonal deletion, whereas the addition of purified B cells to adherent cells restored tolerance inducibility. It was further shown that a combination of CBA/J B cells and C3H/He dendritic cells was effective in eliminating Mls-reactive clones. These results indicate that for the deletion of clones reactive with Mls antigens during T cell development in the thymus, both DC and B cells are required.

Sign in / Sign up

Export Citation Format

Share Document