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Results for “CD3 Complex”

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PubMed1998

Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes.

Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8(+) lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.

Animals↗

PubMed2004

Late onset of treatment with a chemokine receptor CCR1 antagonist prevents progression of lupus nephritis in MRL-Fas(lpr) mice.

Slowly progressive renal injury is the major cause for ESRD. The model of progressive immune complex glomerulonephritis in autoimmune MRL(lpr/lpr) mice was used to evaluate whether chemokine receptor CCR1 blockade late in the disease course can affect progression to renal failure. Mice were treated with subcutaneous injections of either vehicle or BX471, a nonpeptide CCR1 antagonist, three times a day from week 20 to 24 of age [corrected]. BX471 improved blood urea nitrogen levels (BX471, 35.1 +/- 5.3; vehicle, 73.1 +/- 39.6 mg/dl; P < 0.05) and reduced the amount of ERHR-3 macrophages, CD3 lymphocytes, Ki-67 positive proliferating cells, and ssDNA positive apoptotic cells in the interstitium but not in glomeruli. Cell transfer studies with fluorescence-labeled T cells that were pretreated with either vehicle or BX471 showed that BX471 blocks macrophage and T cell recruitment to the renal interstitium of MRL(lpr/lpr) mice. This was associated with reduced renal expression of CC chemokines CCL2, CCL3, CCL4, and CCL5 and the chemokine receptors CCR1, CCR2, and CCR5. Furthermore, BX471 reduced the extent of interstitial fibrosis as evaluated by interstitial smooth muscle actin expression and collagen I deposits, as well as mRNA expression for collagen I and TGF-beta. BX471 did not affect serum DNA autoantibodies, proteinuria, or markers of glomerular injury in MRL(lpr/lpr) mice. This is the first evidence that, in advanced chronic renal injury, blockade of CCR1 can halt disease progression and improve renal function by selective inhibition of interstitial leukocyte recruitment and fibrosis.

Animals↗

PubMed2004

IL-2 and IL-10 production by human CD4+T cells is differentially regulated by p38: mode of stimulation-dependent regulation of IL-2.

Antigenic stimulation of T cells initiates a complex series of intracellular signaling pathways that target and activate different cytokine genes. The participation of mitogen-activated protein kinases (MAPKs) in these processes has not been studied thoroughly and in some instances conflicting results have been reported. Here we have examined the role of p38 MAPK on IL-2 and IL-10 production following activation of human CD4+ T cells or of the leukemic cell line Hut-78, with either plate-bound anti-CD3 in the presence or absence of soluble anti-CD28 (plCD3, plCD3/sCD28), or with cross-linked anti-CD3 and anti-CD28 (crsCD3+CD28), or with PMA plus ionomycin. Pharmacological inhibition of the p38 pathway with either SB203580, SB202190, or SKF86002 strongly downregulated IL-10 production by T cells stimulated with any of the above treatments. In contrast the effect of p38 inhibition on IL-2 was stimulus dependent. Thus, p38 inhibition strongly upregulated IL-2 production (up to 10-fold) in the plCD3- and plCD3/sCD28-stimulated cultures while it had minimal or no effect in the other two stimulation protocols. Intracellular and mRNA levels of IL-2 and IL-10 were also upregulated and downregulated, respectively, by p38 inhibitors in the plCD3/sCD28-stimulated CD4+ T cells. Also, the induction of IL-2 and the parallel suppression of IL-10 by p38 inhibitors were independent of the balance between these two cytokines, as demonstrated by the addition of exogenous IL-10 or blocking anti-IL-10 antibody in CD4+ and Hut-78 cell cultures. These results show that p38 acts as a molecular switch that changes the balance between IL-2 and IL-10. This is especially important considering the opposing role of these cytokines in peripheral immune tolerance.

Antibodies↗

PubMed1990

CD45 ligation in T cells regulates signal transduction through both the interleukin-2 receptor and the CD3/Ti T-cell receptor complex.

The cytoplasmic domain of the CD45 leukocyte cell surface antigen has recently been shown to possess protein tyrosine phosphatase (PTPase) activity. The existence of a cell membrane-bound PTPase may represent a mechanism by which an activation signal, initiated by ligand binding to a surface receptor, is down-regulated following delivery of the signal. Both the interleukin-2 (IL2) growth factor receptor and the CD3/Ti T-cell antigen receptor contain a subunit which is phosphorylated on tyrosine by an activated protein kinase (PTK) during T-cell activation. We compared the effect of CD45 ligation on signal transduction mediated by the binding of IL2 or anti-CD3 to these two receptors. Immunoblotting with anti-phosphotyrosine antiserum was used to investigate the effect of CD45 ligation on anti-CD3- or IL2-induced protein tyrosine phosphorylation. When CD3 and CD45 were triggered together, changes in the pattern of tyrosine phosphorylation of specific substrates was observed in comparison to the stimulus triggered through CD3 alone. In contrast, CD45 ligation did not alter the pattern of tyrosine-phosphorylated proteins in "resting" T-cell blasts responding to IL2, except for a mobility shift of a 55 kDa protein and increased phosphorylation of a 112 kDa substrate. The proliferative response of T cells to both anti-CD3 or IL2 was inhibited by ligating CD45. The CD45 molecule down-regulated CD3-induced T-cell activation when the CD45 and CD3 molecules were ligated simultaneously with immobilized antibodies. In contrast, immobilized CD45 mAb alone inhibited IL2-induced proliferation, and the inhibition was not potentiated by simultaneously using a CD25 mAb which was non-competitive for IL2-binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1994

Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis.

Experiments were designed to test the hypothesis that chronic exposure to tumor necrosis factor alpha (TNF) alters the function of activated T lymphocytes. Pretreatment of tetanus toxoid-specific T cell clones with TNF for up to 16 d impaired rechallenge proliferative responses to antigen in a dose- and time-dependent fashion. IL-2 and PHA responses were preserved. Prolonged treatment with TNF impaired production of IL-2, IL-10, IFN gamma, TNF, and lymphotoxin (LT) following stimulation with immobilized OKT3, and resulted in suboptimal expression of the IL-2R alpha chain (Tac) but not CD3, CD4, or HLA-DR antigens, when compared to untreated control cells. By contrast, pretreatment of T cells for prolonged periods in vitro with neutralizing anti-TNF monoclonal antibodies (mAb) enhanced proliferative responses, increased lymphokine production, and upregulated Tac expression following stimulation with OKT3. To determine whether TNF exerts immunosuppressive effects on T cells in vivo, we studied cell-mediated immunity in patients with active rheumatoid arthritis (RA), before and after treatment with a chimeric anti-TNF mAb. Treatment with anti-TNF restored the diminished proliferative responses of PBMC to mitogens and recall antigens towards normal in all patients tested. These data demonstrate that persistent expression of TNF in vitro and in vivo impairs cell-mediated immune responses.

Antibodies, Monoclonal↗

PubMed1990

Selection of T cell receptor expression mutants through the functionally linked Ly-6A.

Ly-6A is a glycosyl-phosphatidylinositol (GPI)-anchored molecule that participates in murine T cell activation. Activation of T cell hybridomas with anti-Ly-6A monoclonal antibody (mAb) leads to production of interleukin-2 (IL-2), but also to a paradoxical growth inhibition, which was used to select for signaling mutants. Fifteen subclones derived from two independent mutageneses and anti-Ly-6A selection were characterized. Thirteen subclones responded poorly or not at all to soluble anti-Ly-6A mAb. Although the selective pressure was exerted through Ly-6A, only one mutant did not express the Ly-6A antigen. Interestingly, 10 of the 15 subclones expressed either nondetectable or a very low level of T cell receptor/CD3 complex (TCR/CD3). Preferential expansion of TCR/CD3 expression mutants following anti-Ly-6A selection further established functional linkage between Ly-6A and TCR/CD3 complex. The mechanism of the functional coupling was investigated by analyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), one of the early events in T cell activation. We showed that PIP2 was not hydrolyzed in response to anti-Ly-6A in TCR/CD3-negative mutants. Aluminum fluoride, which activates G protein directly, did induce PIP2 hydrolysis in these cells. These data suggest that activation signals originated from Ly-6A must be transmitted first to TCR/CD3 complex, which then couples to the G protein/phospholipase C system. A similar requirement also applies to the Thy-1 protein and lectin receptors. Thus, the TCR/CD3 complex plays a central role in the integration and transmission of activation signals that originated from several T cell surface molecules.

Aluminum↗

PubMed1991

T-cell development and transmembrane signaling: changing biological responses through an unchanging receptor.

The antigen receptor repertoire is conditioned by discriminating forces in the thymus. Cells that see antigen only in the context of self major histocompatibility gene products are positively selected and those that recognize self antigens are deleted. The molecular mechanisms by which this complex conditioning is achieved via a single antigen receptor is one of the most fascinating problems in immunology. Here Terri Helman Finkel and colleagues review the literature and present a unifying mechanistic model of this process.

Animals↗

PubMed1997

Treatment with anti-LFA-1 alpha monoclonal antibody selectively interferes with the maturation of CD4- 8+ thymocytes.

Maturation of T lymphocytes in the thymus is driven by signals provided by soluble factors and by the direct interaction between thymocytes and stromal cells. Although the interaction between T-cell receptor (TCR) and major histocompalibility complex (MHC) molecules on stromal cells is crucial for T-cell development, other accessory molecules seem to play a role in this process. In order to better understand the role of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) molecules in thymocyte maturation, mice were treated from birth with saturating doses of non-cytolytic-specific monoclonal antibodies. The effect of this treatment on thymocyte subpopulations and the expression of CD3 and TCR-alpha beta by these cells was investigated by flow cytometry. Our data demonstrated that the effective saturation of LFA-1 alpha chain in the thymus, but not ICAM-I or LFA-I beta chain, selectively interfered with the maturation of CD8+ T cells, as manifested by a marked reduction in the frequency of CD4-8+ thymocytes expressing high levels of CD3 and TCR-alpha beta. This selective reduction was also observed in peripheral blood mononuclear cells and spleen cells. The analysis of the frequencies of various V beta TCR showed that CD4-8+ thymocytes were globally affected by the treatment. These results underline the importance of the interaction between LFA-1 and its ligands in the maturation of CD8+ T cells and document the existence of different molecular requirements for the differentiation of CD4+ and CD8+ T cells.

Animals↗

PubMed2005

CD28 regulates the translation of Bcl-xL via the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway.

In concert with the TCR, CD28 promotes T cell survival by regulating the expression of the antiapoptotic protein Bcl-x(L). The mechanism by which CD28 mediates the induction of Bcl-x(L) remains unknown. We show that although signaling through the TCR is sufficient to stimulate transcription of Bcl-x(L) mRNA, CD28, by activating PI3K and mammalian target of rapamycin, provides a critical signal that regulates the translation of Bcl-x(L) transcripts. We observe that CD28 induced 4E-binding protein-1 phosphorylation, an inhibitor of the translational machinery, and that CD28 costimulation directly augmented the translation of a Bcl-x(L) 5'-untranslated region reporter construct. Lastly, costimulation by CD28 shifted the distribution of Bcl-x(L) mRNA transcripts from the pretranslation complex to the translationally active polyribosomes. These results demonstrate that CD28 relieves the translational inhibition of Bcl-x(L) in a PI3K/mammalian target of rapamycin-dependent manner.

Animals↗

PubMedDate not supplied

Signal transduction in T lymphocytes.

T lymphocytes utilize a variety of surface receptors to transmit environmental signals across the plasma membrane and initiate biochemical events leading to responses such as proliferation, anergy, cytokine secretion, and death. The T cell receptor complex, CD28, IL-2 receptor, and CD95 each couple to distinct sets of cytoplasmic signaling events to modulate the biological responses of T cells. Deficiency or defective function of proteins involved in signaling through these receptors are associated with murine and human disease.

Animals↗

PubMed1992

Costimulation of T cell receptor/CD3-mediated activation of resting human CD4+ T cells by leukocyte function-associated antigen-1 ligand intercellular cell adhesion molecule-1 involves prolonged inositol phospholipid hydrolysis and sustained increase of intracellular Ca2+ levels.

Activation of resting human CD4+ T cells mediated by mAb ligation of the TCR/CD3 complex requires costimulatory signals to result in proliferation; these can be provided by intercellular cell adhesion molecule-1 (ICAM-1, CD54) a natural ligand of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18). We analyzed early signaling events involved in T cell activation to determine the contribution by the LFA-1/ICAM-1 interaction. We studied in detail the hydrolysis of phosphatidylinositol(4,5)bisphosphate and intracellular levels of free Ca2+ during stimulation with beads coated with the CD3 mAb OKT3 alone or in combination with purified ICAM-1 protein. Our investigations show no response to LFA-1/ICAM-1 alone, but that costimulation by LFA-1/CAM-1 interaction induces prolonged inositol phospholipid hydrolysis (up to 4 h), resulting in generation of both inositol(1,4,5)phosphate3 and inositol(1,3,4,5)phosphate4 and their derivatives. Based on studies with cycloheximide, this costimulatory effect of prolonged inositol phospholipid hydrolysis appears dependent in part on de novo protein synthesis. A sustained increase in intracellular levels of free Ca2+ level is also observed after LFA-1/ICAM-1 costimulation, which is at least partly dependent on extracellular sources of Ca2+. Kinetic studies indicate that costimulation requires a minimal period of 4 h of LFA-1/ICAM-1 interaction to provide maximal costimulation for OKT3-mediated T cell proliferation. Thus, the necessary costimulation required for OKT3-mediated proliferation in this model system may be provided by an extended LFA-1/ICAM-1 interaction that in combination with OKT3 mAb leads to signal-transducing events, resulting in prolonged phospholipase C activation and phosphatidylinositol(4,5)bisphosphate hydrolysis, and a sustained increase in intracellular levels of free Ca2+.

CD4-Positive T-Lymphocytes↗

PubMed1992

Does co-aggregation of the CD45 and CD3 antigens inhibit T cell antigen receptor complex-mediated activation of phospholipase C and protein kinase C?

The binding of agonistic monoclonal antibodies (mAb) to the CD3 antigen in T cells induces a rapid increase in tyrosine phosphorylation, inositive phosphate (IP) production, a rise in intracellular calcium and protein kinase C (PKC) activation. These intracellular signals have been implicated in the control of interleukin-2 and interleukin-2R receptor gene expression, thereby regulating T cell proliferation. Previous studies have shown that co-ligation of the CD45 and CD3 antigens inhibits CD3-induced tyrosine phosphorylation, IP production, calcium signals and T cell proliferation. It has therefore been suggested that the CD45 antigen uncouples the T cell receptor (TcR) from mitogenic signal pathways. In this study co-ligation of the CD3 and CD45 antigens with precisely constructed bispecific mAb did not inhibit CD3-induced T cell proliferation, IP production, calcium signals, diacylglycerol production or PKC activation. Furthermore, co-ligation of CD3 and CD45 antigens already cross-linked with IgM mAb did not lead to inhibition of CD3-induced calcium signals. Inhibitions of CD3-induced intracellular signals were observed following co-ligation of IgG CD45 and CD3 mAb with anti-IgG (F(ab')2 fragments. However, comparable inhibitions were also noted following co-ligation of CD3 with other abundant cell-surface antigens such as CD5 and LFA-1, and inhibitions were only observed when the CD3 mAb used required cross-linking to induce signals. These results suggested that the inhibitory effects of CD45 IgG mAb were not specific and were caused by the prevention of CD3-CD3 cross-linking following CD3 antigen co-ligation with other cell surface molecules. These findings are inconsistent with a specific inhibitory role for the CD45 phosphotyrosine phosphatase in uncoupling the TcR from mitogenic signal pathways.

Antibodies, Monoclonal↗

PubMed1992

TcR-alpha mRNA accumulation does not dictate cell surface TcR/CD3 expression.

The TcR-alpha chain is the last subunit of the TcR/CD3 complex to be expressed during thymic ontogeny. Since the presence of all subunits are required for efficient expression of this complex on the cell surface, this has lead to the hypothesis that the TcR-alpha chain is the limiting subunit which controls cell surface TcR/CD3 expression during thymocyte differentiation. We have examined this issue using a T-lymphoma cell clone, RS4.2, which has a CD4- CD8- Thyl+ J11d+ IL2R+ phenotype, identical with immature thymocytes which have the capacity to generate all major T cell subsets. The RS4.2 cell clone accumulates abundant amounts of TcR-beta, CD3-gamma, -delta, -epsilon and -zeta transcripts, but expresses trace levels of TcR-alpha transcripts and cell surface TcR/CD3. TcR-alpha mRNA levels can be dramatically augmented in RS4.2 cells by three distinct mechanisms: in response to treatment with either phorbol myristate acetate (PMA), calcium ionophore (A23187), or cycloheximide (CHX). However, the expression of TcR/CD3 on the cell surface fails to be increased by any of these agents. In fact, PMA induces a rapid down-regulation of cell surface TcR/CD3 expression. In contrast, these agents trigger an increase in cell surface IL2R expression which coincides with augmented IL2R-alpha mRNA levels. Thus, in RS4.2 cells, IL2R surface expression is controlled by transcript levels, while TcR/CD3 surface expression is regulated by post-transcriptional events, independent of TcR-alpha mRNA accumulation.

Antigens, Differentiation, T-Lymphocyte↗

PubMed2006

Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates.

p97/VCP associated with Ufd1-Npl4 is considered a key player in ER-associated degradation (ERAD). RNA interference (RNAi) of one component of the Ufd1-Npl4 heterodimer destabilizes the VCP-Ufd1-Npl4 complex inducing proteasome-dependent degradation of the other component and releasing free VCP. In contrast to RNAi of VCP, RNAi of Ufd1 or Npl4 depleting approximately 90% of the VCP-Ufd1-Npl4 complexes does not induce unfolded protein response, indicating that the Ufd1-Npl4 dimer is not involved in the regulation of ER function by VCP. RNAi of Ufd1 or Npl4 is associated with a 2-fold increase in the levels of polyubiquitinated proteins, which form dispersed aggregates often associated with calnexin-positive structures. However, contrary to the effects of proteasome inhibition, RNAi of Ufd1 or Npl4 does not induce an accumulation of alpha-TCR and delta-CD3, two ERAD substrates overexpressed in HeLa cells. Instead, a 60-70% decrease in their levels is observed. The decrease in alpha-TCR levels is associated with a 50% decrease of its half-life. Upregulation of the putative channel forming protein, derlin-1, may contribute to the increased degradation of ERAD substrates. To explain our findings, we propose a model, where association of emerging ERAD substrates with VCP-Ufd1-Npl4 is not required for their degradation but has a regulatory role.

Adaptor Proteins, Vesicular Transport↗

PubMed1992

Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.

Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression.

Antibodies, Monoclonal↗

PubMed2001

Changes in the T cell receptor macromolecular signaling complex and membrane microdomains during T cell development and activation.

Initiation and propagation of T cell receptor signaling pathways involves the mobilization and aggregation of a variety of signaling intermediates with the T cell receptor and associated molecules into specialized signaling complexes. Accumulating evidence suggests that differential regulation of the formation and composition of the T cell receptor macromolecular signaling complex may affect the different biological consequences of T cell activation. The regulatory mechanisms involved in the assembly of these complexes remains poorly understood, but in part is affected by the avidity of the T cell receptor ligand, co-stimulatory signals, and by the differentiation state of the T cell.

CD4 Antigens↗

PubMed2003

A serine/threonine phosphorylation site in the ectodomain of a T cell receptor beta chain is required for activation by superantigen.

The presence of consensus phosphorylation sites in the ectodomains of cell surface proteins suggests that such post-translational modification may be important in regulation of surface receptor activity. To date, the only cell surface receptor for which such ectodomain phosphorylation has been conclusively demonstrated is the clonally expressed T cell antigen receptor (TCR). Attempts to conclusively identify individual phosphorylated residues in TCR alpha and beta chains and determine their functional significance by biochemical approaches failed due to insufficient quantities of purified molecules. Here we present the results of an alternative approach where survey of phosphorylation sites in the TCR alpha and beta chains was accomplished using site-directed mutagenesis and retroviral vector expression, as well as in vitro phosphorylation of synthetic peptide substrates. All mutants studied directed the cell surface expression of normal amounts of TCR, and all transfectants could be stimulated to produce IL-2 in response to substrate-immobilized antibody to TCR. However, mutation of serine-88 in the protein kinase A phosphorylation site of the TCR beta chain resulted in a complete lack of response to the superantigen staphylococcal enterotoxin B (SEB). In addition, this mutation abolished TCR-associated tyrosine phosphorylation, consistent with the impairment of cell signaling. Reversion of the serine-88/alanine mutation with phosphorylatable threonine completely restored the SEB recognition by TCR. These results, interpreted in the context of the known three-dimensional structure of the complex of SEB and TCR, are consistent with the view that serine-88 is important for the contact of the TCR beta chain with SEB.

Amino Acid Sequence↗

PubMed2002

Thymocyte apoptosis induced by T cell activation is mediated by glucocorticoids in vivo.

Glucocorticoids, administered in pharmacological doses, potently modulate immune system function and are a mainstay therapy for many common human diseases. Physiologic production of glucocorticoids may play a role in optimization of the immune repertoire both centrally and peripherally. Possible effects include alteration of lymphocyte development and down-regulation of cytokine responses, but essential roles remain unclear. To determine the part that endogenous glucocorticoids play in thymocyte development, we used fetal liver from mice lacking the glucocorticoid receptor GRko for immunological reconstitution of lethally irradiated wild-type (WT) mice. We find normal numbers and subset distribution of GRko thymocytes. GRko thymocytes also exhibit similar sensitivity to apoptosis induced by activating anti-CD3epsilon Ab as WT thymocytes in vitro. Surprisingly, GRko thymocytes are significantly more resistant than WT thymocytes to anti-CD3epsilon-mediated thymocyte apoptosis in vivo. Consistent with this finding, in vivo TCR complex activation induces sustained high levels of glucocorticoids that correlate strongly with thymocyte apoptosis in WT mice. We find that while direct engagement of the TCR complex may cause death of a subset of thymocytes, glucocorticoids are required for deletion of the majority of thymocytes. Thus, TCR stimulation by Ab administration may more accurately reflect polyclonal T cell activation than negative selection in vivo.

Animals↗