scholarly journals Demonstration of functional CD40 in B-lineage acute lymphoblastic leukemia cells in response to T-cell CD40 ligand

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5162-5170 ◽  
Author(s):  
N Renard ◽  
M Lafage-Pochitaloff ◽  
I Durand ◽  
V Duvert ◽  
L Coignet ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Clone ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Activated T Cells ◽  
T Cell Clone ◽  
B Lineage

Because activated T cells were previously shown to induce proliferation of human normal B-cell precursors (BCP) via the CD40 pathway, we investigated the effects of T cells on leukemic blasts isolated from patients with B-lineage acute lymphoblastic leukemia (BCP-ALL). An anti- CD3 activated human CD4+ T-cell clone was found to induce significant call proliferation in four of nine BCP-ALL samples analyzed. In one of these cases, the T-cell effect was clearly dependent on interaction between CD40 and its ligand. Accordingly, a more thorough analysis was performed on this particular leukemia (case 461, adult early pre-B-ALL, mBCR+, Philadelphia+, i(9q)+). Thus, autologous CD4+ T cells isolated from the patient were also able to induce CD40-dependent proliferation of the leukemic blasts. Analysis of the phenotype after coculture showed that, among the CD19+ cells, a proportion gradually lost expression of CD10 and CD34, whereas some cells acquired CD23. In addition, and in contrast with normal BCP, activated T cells promoted maturation of a subset of the case 461 leukemic cells into surface IgM+ cells. The leukemic origin of the cycling and the maturing cells was assessed by the presence of i(9q), a chromosomal abnormality associated with this leukemia and evidenced by fluorescence in situ hybridization. Taken together, these results show that leukemic BCP can be activated via CD40 but that not all cases display detectable stimulation in response to T cells despite their expression of CD40. In addition, the present data suggest that CD4+ T cells could potentially play a role in the physiology of BCP-ALL.

A “non-fratricidal” αβ- T Cell Receptor That Targets Survivin Expressed By Hematological Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 141-141
Author(s):  
Caroline Arber ◽  
Xiang Feng ◽  
Harshal Abhyankar ◽  
Helen E. Heslop ◽  
Malcolm K. Brenner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Cell Clone ◽  
Cell Receptor ◽  
Activated T Cells ◽  
T Cell Clone ◽  
Myeloid Leukemias

Abstract Survivin is broadly expressed by hematological malignancies as well as by solid tumors and may be a suitable target for T-cell immunotherapy. Previously, the utility of this target has been challenged by the occurrence of “fratricide” when T cells expressing a high avidity survivin-specific T cell receptor (TCR) killed each other because survivin epitopes can be presented by the T cells themselves (Leisegang M et al, J Clin Invest. 2010 Nov;120(11):3869-77). To overcome this obstacle, we used limiting dilution to isolate a new T-cell clone targeting the HLA-A*02-restricted survivin epitope ELT (survivin95-104) and its variant LML (survivin96-10497M) starting from autologous cultures, rather than from the allogeneic cultures previously used for this approach. In 51Chromium (Cr)-release assays, this T-cell clone, with nanomolar avidity, displayed specific killing against the survivin+HLA-A*02+ leukemia cells BV173 (39±16% specific lysis, E:T 40:1) and multiple myeloma cells U266 (20±7%) but not against HLA-A*02– HL-60 cells (2±2%). Furthermore, the colony formation of primary myeloid leukemias was inhibited (>50% reduction) while that of healthy bone marrow (BM) was unaffected. The TCR α- and β-chains were then cloned in an optimized retroviral vector that was used to transduce CD8+ T cells which then efficiently expressed the transgenic αβTCR (89±4%, n=6). As compared to non-transduced (NT) T cells, survivin-αβTCR+ T cells produced significant lysis of BV173 (46±14% vs 8±6%, E:T 20:1, n=12, p<0.001) and U266 (27±12% vs 14±6%, p=0.003) but not of HL-60 (14±7 vs 14±6 %, p=NS). Blocking the target cells with specific anti-MHC class I antibodies confirmed the HLA-restriction of TCR transgenic T cells. Importantly, transgenic cells recapitulated the function of the original clone by inhibiting colony formation (range 32-78% reduction, n=5) of primary myeloid leukemias while preserving normal clonogenic capacity of healthy BM or cord blood (n=5). When tested in vivo in a xenograft model of established systemic acute leukemia (FFLuc+BV173) using bioluminescent imaging, leukemia progression was significantly slower in mice treated with survivin-αβTCR+ versus NT T cells (40x106 ± 71x106 vs. 128 x 106 ± 176 x 106 photons/sec by day 28) (p=0.04) and survival improved (n=12/group, p=0.01). This effect was even more pronounced when T cells were transferred to mice with limited leukemia burden (bioluminescent signal by day 40: 8.1 x 106 ± 9 x 106 vs. 195 x 106 ± 85 x 106 photons/sec) (p=0.003, n=10/group). Overall survival was improved by day 80 (p<0.001) and 3/10 mice treated with TCR+ T cells completely cleared the leukemia. Crucially, the TCR cloned from our autologous culture system produced no fratricidal activity in 51Cr-release assays against HLA-A*02+ activated T cells (1±2%, E:T 20:1, n=7). Activated T cells were only killed by TCR+ T cells when they were also pulsed with survivin peptides (46±12% for LML, 68±14% for ELT, n=7). To elucidate at the molecular level why our “autologous” TCR had selective antitumor activity unlike the fratricidal activity of “allogeneic” TCRs (Leisegang M et al, J Clin Invest. 2010 Nov;120(11):3869-77), we modeled the structure of each TCR-peptide-HLA ternary complex using the Rosetta software. While the overall binding energies of TCR-peptide-HLA interfaces for both TCRs were similar, the “autologous” TCR showed a 48% higher binding energy contribution for the peptide as compared to the fratricidal TCR, whose interaction was primarily with the HLA molecule rather than with the survivin peptide in the HLA-binding groove. In conclusion, we have cloned a novel survivin-TCR with a highly epitope-specific binding mode that can be efficiently expressed in polyclonal T cells and provides antitumor activity in vitro and in vivo without affecting the survival of T cells or normal hematopoietic progenitors. Our results indicate that maximal recognition of the peptide presented in the HLA groove is critical for TCR selectivity. Disclosures: Heslop: Celgene: Patents & Royalties; Cell Medica: Patents & Royalties. Brenner:Celgene: Patents & Royalties, Research Funding. Dotti:Celgene: Patents & Royalties, Research Funding. Savoldo:Celgene: Patents & Royalties, Research Funding.

scholarly journals A novel SIV gag-specific CD4+T-cell clone suppresses SIVmac239 replication in CD4+T cells revealing the interplay between antiviral effector cells and their infected targets

Virology ◽  
2016 ◽  
Vol 493 ◽  
pp. 100-112 ◽  
Author(s):  
Victor I. Ayala ◽  
Matthew T. Trivett ◽  
Lori V. Coren ◽  
Sumiti Jain ◽  
Patrick S. Bohn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Clone ◽  
Cd4 T Cell ◽  
Effector Cells ◽  
T Cell Clone

scholarly journals Mildly oxidized low-density lipoproteins suppress the proliferation of activated CD4+ T-lymphocytes and their interleukin 2 receptor expression in vitro

1998 ◽  
Vol 330 (2) ◽  
pp. 659-666 ◽  
Author(s):  
Sylvie CASPAR-BAUGUIL ◽  
Majed SAADAWI ◽  
Anne NEGRE-SALVAYRE ◽  
Mogens THOMSEN ◽  
Robert SALVAYRE ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Clone ◽  
Peripheral Blood Lymphocytes ◽  
Cd4 T Cell ◽  
Activated T Cells ◽  
T Cell Clone ◽  
Activated T Lymphocytes

Activated T-lymphocytes are present in early atherosclerotic lesions where they may interact with oxidized low-density lipoproteins (oxLDLs). In this study the non-specific effect of oxLDLs on the activation of T-cells in vitro was investigated. LDLs were oxidized by UV irradiation and characterized by a low level of lipid peroxidation and only slight apolipoprotein B modification. Peripheral blood lymphocytes from normal individuals were stimulated in vitro with the polyclonal activator phytohaemagglutinin in the presence of various doses of LDLs and oxLDLs. LDLs enhanced the proliferation of peripheral blood lymphocytes at doses up to 100 μg/ml but were inhibitory at 200 μg/ml, whereas low doses of oxLDLs (over 10 μg/ml) inhibited the proliferation. OxLDLs also inhibited the proliferative responses of an alloreactive CD4+ T-cell line immortalized by Herpes virus saimiri and an influenza haemagglutinin-specific CD4+ T-cell clone. Viability tests using Trypan Blue exclusion or expression of Apo2.7, an apoptosis marker, did not indicate any significant cell death at doses up to 100 μg/ml oxLDL. At this concentration, cell-cycle analysis showed an accumulation of cells at the G1/S interface in the CD4+ cell clone, without significant DNA fragmentation. The expression of the activation antigen CD25 on T-lymphocytes (on phytohaemagglutinin-activated T-cells and on CD4+ T-cell clone), requisite to the commitment of activated T-cells from G1 phase to S phase, was also inhibited by oxLDLs whereas expression of other activation antigens such as CD69 and HLA-DR was unchanged. In conclusion, these data show that mildly oxidized LDLs inhibit the proliferation and CD25 expression of activated T-lymphocytes and suggest that oxLDLs may slow down the T-cell response in atherosclerotic lesions.

scholarly journals The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling

2003 ◽  
Vol 162 (4) ◽  
pp. 673-682 ◽  
Author(s):  
Joseph Lin ◽  
Arthur Weiss
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Activated T Cells ◽  
Phosphatase Domain ◽  
T Cell Clone ◽  
Immunologic Synapse

CD148 is a receptor-like protein tyrosine phosphatase up-regulated on T cells after T cell receptor (TCR) stimulation. To examine the physiologic role of CD148 in TCR signaling, we used an inducible CD148-expressing Jurkat T cell clone. Expression of CD148 inhibits NFAT (nuclear factor of activated T cells) activation induced by soluble anti-TCR antibody, but not by antigen-presenting cells (APCs) loaded with staphylococcal enterotoxin superantigen (SAg) or immobilized anti-TCR antibody. Immunofluorescence microscopy revealed that the extracellular domain of CD148 mediates its exclusion from the immunologic synapse, sequestering it from potential substrates. Targeting of the CD148 phosphatase domain to the immunologic synapse potently inhibited NFAT activation by all means of triggering through the TCR. These data lead us to propose a model where CD148 function is regulated in part by exclusion from substrates in the immunologic synapse. Upon T cell–APC disengagement, CD148 can then access and dephosphorylate substrates to down-regulate prolongation of signaling.

scholarly journals Decoding Clonal Evolution in Relapsed T Cell Acute Lymphoblastic Leukemia at Single Cell Resolution

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3482-3482
Author(s):  
Jingliao Zhang ◽  
Yongjuan Duan ◽  
Yanxia Chang ◽  
Yue Wang ◽  
Chao Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Single Cell ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
The Other ◽  
Leukemic Cells

Abstract T-lineage acute lymphoblastic leukemia (T-ALL) comprises approximately 10-15% of pediatric ALL cases with distinct feature in biology and largely inferior outcome compared to B-ALL. Growing evidence has reflected pivotal roles of clonal evolution in T-ALL recurrence, but bulk sequencing may not serve as the perfect model to reliably infer clonal heterogeneities and their immunomodulatory milieu during leukemia development. In this study, single-cell sequencing was applied to uncover leukemic clonal relationships with relapse throughout chemotherapy in T-ALL at a more accurate resolution. We performed bulk whole-exome sequencing for sorted CD7 + BMMCs from 5 pairs of diagnosis-relapse (Dx_Rel) samples, revealing a series of well-reported hotspot mutations in T-ALL. Among those, we observed diagnosis-specific variations and relapse-emerged variations, suggesting the putative correlations with chemo-resistance. Transcriptomic sequencing highlighted additional stemness and metabolic abnormalities underlying leukemic re-occurrence. Incorporated Dx_Rel paired ATAC-seq depicted relapse-specific activated chromatin regions, such as ELK1, ELK4, RUNX1. To dissect clonal diversities within and across the 5 Dx_Rel T-ALL pairs, we carried out high-throughput droplet-based 5'-single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (scTCR-seq). By performing unsupervised clustering of scRNA-seq profiles encompassing 10 samples, we identified 23 distinct T-lineage clusters (Cluster 0-22) based on the two-dimensional UMAP visualization. In 2 out of 5 patients (T593 and T788), diffusion map of T-lineage sub-clusters between diagnostic and relapsed samples appeared to be almost identical, while distinct shifts from diagnosis to relapse in the compositions have been observed in the other 3 out of 5 patients (T956, T723 and T856). Besides, it was noteworthy that two T-cell sub-clusters were concluded as "normal" T cells (Cluster 9 and 12) uniformly presented in both diagnostic and relapsed diffusion of T-cell sub-clusters across 5 Dx_Rel, from which TCR repertoires and expression profiles could well discriminate leukemic cells. Next, we sought to further deconvolute the clonal evolution patterns for T-ALL Dx_Rel pairs. We observed that except in T788 lacking of clonal TCRs, dominant diagnostic clones of the other 4 patients diminished (T593) or vanished (T956, T723, T856) at relapse, sparing newly emerged subclones predominantly substituted at relapse. We clearly depicted two distinct patterns of evolutionary trajectories in these 4 Dx_Rel pairs by comprehensively mapping hierarchical TCR clonotypes onto leukemic clonotypes at single cell levels. Specifically, in T956 and T723, we observed significant outgrowth of incidental diagnostic sub-clones at relapse, whereby surrogate TCR repertoires correspondingly enumerated, suggestive of dynamic shifts in dominant clone over continuous chemo-exposure. Whereas in T593 and T856, expanding clones at relapse were showed up with completely different gene signatures from the diagnostic ones, but dominant clones at diagnosis and relapse were surprisingly presented with identical TCR repertoires. This was undoubtedly informative of leukemic "clonal drift" within which hypothetical intrinsic transformation happened to the same subclones over persistent chemotherapy. Besides, we took advantage of our well-discriminated model to fully delineated the involvement of "normal" T subclusters in leukemic latency and chemo-responsiveness. By analyzing TCR repertoires in combined with expression profiles, we noted that "normal" T cells infiltrated by T-ALL were majorly distributed in CD8-effector sub-clusters compared to those from healthy donor, suggesting a robust leukemic stimulation on effector CD8 signaling in T-ALL microenvironment. Collectively, our presented study accurately distinguished leukemic cells from normal T cells in T-ALL at a single-cell resolution. By tracking transcriptomic profiles within and across Dx_Rel T-ALL pairs, we further identified distinct clonal evolutionary patterns, which may determine diversified fates of leukemic clones in response to therapeutic pressures. In the meantime, we provided a comprehensive phenotypic view on "normal" T cells under leukemic prevalence and re-occurrence, extending significant implications for future precise immunotherapies. Disclosures No relevant conflicts of interest to declare.

scholarly journals TIM-3 Expression on CD4+ Bone Marrow T Cells Predicts Relapse of Pediatric B-Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2833-2833
Author(s):  
Franziska Blaeschke ◽  
Semjon Willier ◽  
Dana Stenger ◽  
Mareike Lepenies ◽  
Martin A. Horstmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Expression Levels ◽  
Pediatric All

Abstract Introduction Pediatric acute lymphoblastic leukemia (ALL) is a cancer entity of minimal mutational load and low immunogenicity. The interaction of ALL cells with bone marrow (BM) T cells has not been investigated as a pathogenic driver or prognostic marker for pediatric ALL. We defined BM T cells of pediatric ALL patients as tumor-infiltrating lymphocytes (TILs) and investigated the prognostic relevance of co-stimulatory and co-inhibitory signals between ALL and BM T cells. Methods BM samples of 100 pediatric ALL patients were analyzed at time of initial diagnosis. T-cell subpopulations and expression of co-stimulatory and co-inhibitory molecules were defined by flow cytometry and correlated with clinical outcome of the patients. To investigate the role of TIM-3 for the interaction between T cells and leukemic cells, CRISPR/Cas9-mediated TIM-3 knockout (KO) was performed in primary T cells by ribonucleoprotein electroporation. T-cell activation and proliferation after contact with leukemic target cells were analyzed in TIM-3 KO cells and compared to wildtype T cells and T cells with retroviral TIM-3 overexpression. Interaction of T cells with leukemic target cells was induced by addition of anti-CD19/-CD3 bispecific T-cell engager (BiTE). Fold change (FC) of T-cell activation and proliferation was analyzed before and after co-culture. BM expression levels of known TIM-3 inducers were identified by RNA next generation sequencing of the bone marrow samples. Results Multivariate analyses identified high TIM-3 expression on CD4+ BM T cells at initial diagnosis as strong predictor for relapse of pediatric acute lymphoblastic leukemia (relapse free survival (RFS) 94.6% vs. 70.3%). The risk to develop ALL relapse was 7.1-fold higher in the group of TIM-3 high expressing patients (n=37) compared to TIM-3 low expressing patients (n=37). Expression levels of known TIM-3 ligands and inducers in the bone marrow of the patients were analyzed by RNA next generation sequencing and compared between patients with high TIM-3 expression (n=12) and low TIM-3 expression (n=15) on BM T cells. Presence of known TIM-3 ligands HMGB1 (High-Mobility-Group-Protein B1) and Galectin-9 was confirmed, but expression levels did not show significant differences. Known TIM-3 inducers IL-2, -7, -15 and -21 were not expressed on RNA level indicating that another mechanism must be responsible for TIM-3 overexpression. In vitro experiments showed that the interaction with leukemic cells induces TIM-3 expression on the surface of T cells (mean TIM-3 expression 51.1% vs. 29.7% on T cells with vs. without addition of leukemic cells, n=3). To investigate the functional relevance of TIM-3 expression in pediatric leukemia, TIM-3 KO and overexpression was performed on primary T cells. TIM-3 KO T cells showed higher activation levels after co-culture with leukemic cell lines plus CD3-/CD19-specific BiTE compared to wildtype (WT) T cells (FC of CD69 surface expression 5.0 vs. 3.2, n=3). FC of anti-leukemic proliferation was impaired in TIM-3 overexpressing T cells compared to WT T cells (FC 1.6 vs. 2.3, n=3) whereas TIM-3 KO T cells showed a higher proliferation FC compared to controls (FC 6.5 vs. 2.4, n=3). Conclusions Our study identifies TIM-3 expression on CD4+ bone marrow T cells at initial diagnosis as a strong predictor for pediatric ALL relapse. TIM-3 expression is induced by interaction of T cells with leukemic cells and results in impaired anti-leukemic T-cell activation and proliferation. TIM-3-mediated T-cell inhibition represents a new mechanism of impaired immune surveillance in pediatric ALL and blockade of this axis may be of importance for future immunotherapy in ALL. Disclosures No relevant conflicts of interest to declare.

CD19/CD3 Bispecific Antibody Blinatumomab (MT-103) Is Highly Effective In Treatment of Patients with Minimal Residual Disease From Chemotherapy-Resistant B-Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 174-174 ◽  
Author(s):  
Max S Topp ◽  
Gerhard Zugmaier ◽  
Nicola Goekbuget ◽  
Svenja Neumann ◽  
Heinz-August Horst ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Clinical Relapse ◽  
B Lineage ◽  
Minimal Residual

Abstract Abstract 174 Blinatumomab, a bispecific, T cell-engaging (BiTE®) antibody, can effectively redirect T cells for highly selective lysis of CD19+ target cells. The B-cell differentiation antigen CD19 is a marker for B-ALL cells. In B-lineage acute lymphoblastic leukemia (ALL), persistence or relapse of minimal residual disease (MRD) is an independent poor prognostic factor, and new treatments are urgently needed. MRD relapse during or after maintenance treatment in adult standard risk patients generally heralds a hematological relapse in 90% of patients. A phase 2 study was conducted to determine the efficacy of blinatumomab in ALL patients with MRD persistence or relapse (MRD level <310-4) after induction and consolidation therapy. MRD was assessed by qRT-PCR for rearrangements of immunoglobulin (Ig) or T-cell receptor (TCR) genes, or for specific fusion genes. Blinatumomab was administered as a 4-week continuous i.v. infusion at a dose of 15 μ g/m2/d followed by a 2-week treatment free period (1 cycle). Primary endpoint was the proportion of patients with MRD response defined by individual rearrarrangement of Ig or TCR below 10-4. Patients who showed neither MRD progression nor response were permitted to receive up to 7 cycles of treatment. Patients who had achieved MRD response received 3 additional consolidation cycles. Between May 2008 and November 2009, 21 patients (16 Ph-negative; 2 patients with MLL-AF4; 5 patients with Ph+ ALL) were enrolled. The cut-off date for data analysis was May 15, 2010. Patients received between 1 and 7 cycles of blinatumomab (total of 66 cycles). Transient pyrexia (100%) and chills (43%) were the most common clinical AEs. There were no blinatumomab related deaths. Sixteen patients became MRD-negative. One patient was not evaluable due to a grade 3 adverse event (AE) leading to treatment discontinuation. Of the responding patients, 13 had never before achieved a negative MRD status on chemotherapy. Regardless of their MRD level prior to study treatment, all 16 (13/15 patients with Ph− and 3/5 patients with Ph+ ALL) became MRD-negative after the first cycle of blinatumomab. Nine patients were enrolled with a MRD load >10-2 prior to study treatment and all reached complete MRD response. Thirteen out of 16 patients with persisting MRD prior to study treatment and 3 out of 4 patients with MRD relapse showed complete MRD response. Overall relapse-free survival (RFS) currently is 78% at a median follow up of 405 days. RFS is 100% for the 8 patients who received subsequent allogeneic stem cell transplantation (median follow up 434 days). Blinatumomab is a highly active treatment for patients with MRD-positive B-lineage ALL after intensive chemotherapy and has an acceptable safety profile. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells in bone marrow that otherwise might cause clinical relapse. A long RFS suggests that blinatumomab may improve outcome in patients with B-precursor ALL. A multicenter international study of blinatumomab in patients with MRD-positive B-lineage ALL has been initiated. Disclosures: Zugmaier: Micromet Inc.: Employment. Degenhard:Micromet Inc.: Employment. Schmidt:Micromet Inc.: Employment. Scheele:Micromet Inc.: Employment. Kufer:Micromet Inc.: Employment. Klinger:Micromet Inc.: Employment. Nagorsen:Micromet Inc.: Employment. Bargou:Micromet Inc.: Consultancy.

scholarly journals IL-2-mediated T cell proliferation in humans is blocked by a monoclonal antibody directed against monomorphic determinants of HLA-DR antigens.

1982 ◽  
Vol 155 (2) ◽  
pp. 599-604 ◽  
Author(s):  
A Moretta ◽  
R S Accolla ◽  
J C Cerottini
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Growth ◽  
Cell Clone ◽  
Direct Interaction ◽  
Activated T Cells ◽  
Human T Cell ◽  
Hla Dr ◽  
Ia Antigens ◽  
T Cell Clone

We have studied the effect on the interleukin (IL-) 2-dependent human T cell growth of two distinct monoclonal antibodies (Mab), D1-12 and 4F2, with specificity for common determinant of human Ia antigens and for a differentiation antigen expressed on all activated T cells, respectively. Strong inhibition of cell growth was found in cultures supplemented with the anti-Ia D1-12 Mab but not in cultures supplemented with 4F2 Mab. These results were obtained when either total mixed leukocyte culture (MLC) T cells or an MLC-derived T cell clone were used as indicator cell systems for IL-2 activity. The inhibition of cell growth appears to be mediated by a direct interaction of D1-12 Mab with the cells and not by a direct inactivation of the growth factor, as addition of the antibody to murine MLC T cells, which do not express the determinant defined by D1-12 Mab, resulted in no inhibition of their proliferation induced by the same source of human IL-2.

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