Fibromodulin as a Novel Tumor-Associated Antigen (TAA) in Chronic Lymphocytic Leukemia (CLL) Which Allows Expansion of Specific CD8+ Autologous T Lymphocytes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 175-175 ◽  
Author(s):  
Christine Mayr ◽  
Dagmar Bund ◽  
Martin Schlee ◽  
Andreas Moosmann ◽  
Michael Hallek ◽  
...  
Keyword(s):  
T Cells ◽  
In Vitro Culture ◽  
B Lymphocytes ◽  
Cd40 Ligand ◽  
Immune Monitoring ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Autologous Tumor ◽  
Tumor Associated Antigen

Abstract BACKGROUND: Fibromodulin (FMOD), a collagen binding protein, was shown to be highly overexpressed in CLL cells compared to normal B lymphocytes by gene expression profiling. Therefore FMOD might serve as potential tumor associated antigen (TAA) in CLL, enabling expansion of FMOD-specific T cells. FMOD is physiologically expressed in articular cartilage, tendon and ligament. Furthermore, interactions of FMOD with the growth factor TGF-b were described and it may be a biologically relevant modulator of TGF-b activity. Methods: Unpulsed native CLL cells and CD40 ligand (CD40L)-stimulated CLL cells as antigen presenting cells (APC) were used to expand autologous T cells from 13 patients. RESULTS: In CLL samples derived from 16 patients, high expression of FMOD by real-time RT-PCR was detectable in contrast to normal B lymphocytes. The number of T cells during four weeks of in vitro culture increased 2-fold with native CLL cells as APC and 3.5-fold with CD40L-stimulated CLL cells as APC. The amount of T cells recognizing HLA-A0201 binding FMOD-derived peptides detected by HLA-A2-dimer/peptide staining increased 10-fold during in vitro culture. The T cells expanded were also able to secrete IFN-g upon recognition of the antigen demonstrated by IFN-g-ELISPOT assays. T cells not only recognized HLA-A0201 binding FMOD peptides presented by TAP-deficient T2 cells, but also FMOD overexpressing autologous CLL cells in an HLA-A0201 restricted manner. Neither HLA-A0201 negative CLL cells nor non-malignant cells, i.e. PBMC from healthy donors or tonsilar B cells, were specifically recognized by T cells. When CD40L-stimulated CLL cells were used as APC, which were pulsed with FMOD peptides prior to coincubation with the T cells, significant higher amounts of T cells specifically recognized autologous CLL cells in IFN-g-ELISPOT assays P< 0.018). CONCLUSION: FMOD was shown for the first time to be naturally processed and ( presented as TAA in primary CLL cells. This enables the expansion of autologous tumor-specific T cells which might be applicable in clinical vaccination trials or as a tool for a CLL-specific immune monitoring in the context of vaccination approaches including CD40L-gene modified autologous leukemic cells.

Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes

Blood ◽  
2005 ◽  
Vol 105 (4) ◽  
pp. 1566-1573 ◽  
Author(s):  
Christine Mayr ◽  
Dagmar Bund ◽  
Martin Schlee ◽  
Andreas Moosmann ◽  
David M. Kofler ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Antigen Processing ◽  
Interferon Γ ◽  
Lymphocytic Leukemia ◽  
Autologous Tumor ◽  
Tumor Associated Antigen ◽  
Ifn Γ

AbstractFibromodulin (FMOD) was shown to be highly overexpressed in chronic lymphocytic leukemia (CLL) cells compared with normal B lymphocytes by gene expression profiling. Therefore FMOD might serve as potential tumor-associated antigen (TAA) in CLL, enabling expansion of FMOD-specific T cells. In CLL samples derived from 16 different patients, high expression of FMOD by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) was detectable in contrast to normal B lymphocytes. We used unpulsed native CLL cells and CD40 ligand (CD40L)–stimulated CLL cells as antigen-presenting cells (APCs) to expand autologous T cells from 13 patients. The number of T cells during 4 weeks of in vitro culture increased 2- to 3.5-fold and the number of T cells recognizing FMOD peptides bound to HLA-A2 dimers increased 10-fold. The expanded T cells also were able to secrete interferon-γ (IFN-γ) upon recognition of the antigen demonstrated by IFN-γ ELISPOT assays. T cells not only recognized HLA-A2–binding FMOD peptides presented by transporter-associated with antigen-processing (TAP)–deficient T2 cells, but also FMOD overexpressing autologous CLL cells in an HLA-A2–restricted manner. In summary, FMOD was shown for the first time to be naturally processed and presented as TAA in primary CLL cells, enabling the expansion of autologous tumor-specific T cells.

In Vitro Expansion of Autologous Follicular Lymphoma-Specific T Cells for Adoptive Transfer.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1482-1482
Author(s):  
Seung-Tae Lee ◽  
Yun Fang Jiang ◽  
Soung-Chul Cha ◽  
Hong Qin ◽  
Larry W. Kwak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Follicular Lymphoma ◽  
Tumor Cells ◽  
Cd4 T Cells ◽  
Cd40 Ligand ◽  
Autologous Tumor ◽  
T Cell Lines

Abstract Advanced stage follicular lymphoma remains an incurable disease with a median survival of 8 to 10 years that has not significantly changed over the last four decades. Therefore, novel treatment options are necessary to improve the clinical outcome in these patients. The observation of spontaneous regressions in a small percentage of patients suggested that augmenting the host immune response could potentially control this malignancy. Strategies using active specific immunotherapy with idiotype vaccines led to induction of clinical and molecular responses in a few patients but have met with only limited success possibly due to the low frequency of antigen-specific T cells induced in the patients. In contrast to active immunization, T cells of a given specificity and function may be selected and expanded in vitro to the desired number for adoptive cell transfer. Towards this goal, we stimulated tumor infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) from five follicular lymphoma patients with CD40 ligand-activated autologous tumor cells at approximately ten-day intervals in the presence of IL-2 and IL-15. After four rounds of stimulations, T cell lines generated from 3/5 patients recognized autologous unmodified tumor cells by producing significant amounts of TNF-α, GM-CSF and/or IFN-γ. By phenotypic analysis, the T cell lines were predominantly CD4+ T cells (&gt; 70%), and intracellular cytokine assay showed that up to 40% of the CD4+ T cells were tumor-reactive. The inhibition of cytokine production by anti-HLA class II but not class I blocking antibodies confirmed that the CD4+ T cells were tumor-reactive. Further characterization revealed that the T cells from one patient recognized autologous tumor but not autologous normal B cells suggesting that they were tumor-specific. While in a second patient CD4+ T cell clones generated from the T cell line by limiting dilution recognized autologous tumor and autologous normal B cells but not autologous monocytes suggesting that they were B cell lineage-specific. We conclude that follicular lymphoma-specific T cells exist and can be efficiently expanded in vitro from both TILs and PBMCs using CD40 ligand-activated autologous tumor cells for adoptive T cell therapy. Additionally, identification of antigens recognized by these T cells could lead to development of novel immunotherapeutic strategies for lymphomas.

Generation of alpha-Type-1 Polarized Dendritic Cells as a Potent Immunogen in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2059-2059 ◽  
Author(s):  
Je-Jung Lee ◽  
Robbie Mailliard ◽  
Ravikumar Muthuswamy ◽  
Kenneth A. Foon ◽  
Pawel Kalinski
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Poly I:C ◽  
Autologous Tumor ◽  
Antigen Uptake ◽  
Gamma Irradiated ◽  
Alpha Type

Abstract We tested the feasibility of generating alpha-type-1 polarized DC (αDC1) from the blood of chronic lymphocytic leukemia (CLL) patients and the in vitro effectiveness of autologous tumor-loaded αDC1s in inducing CTLs against CLL. CD14+ cells were isolated from the peripheral blood of CLL patients and were cultured in rhu GM-CSF and IL-4. On day 6, DC maturation was induced using either a standard cytokine cocktail (in IL-1β, TNFα, IL-6, and PGE2) or αDC1-polarizing cocktail (in IL-1β, TNFα, IFNα, IFNγ, and poly-I:C). In either case, the maturing DCs were loaded with gamma-irradiated autologous CLL cells. αDC1s from CLL patients expressed substantially higher levels of several costimulatory molecules (CD83, CD86, CD80, CD11c and CD40) than standard DCs (sDCs) while CCR7 showed lower expression. Gamma-irradiated CLL cells were more efficienly taken up by DCs compared to UVC-irradiated CLL cells, but the ability of tumor antigen uptake was similar between αDC1 and sDCs. The capacity of IL-12p70 secretion in DCs (baseline and after stimulation with CD40L-transfected J558 cells) was significantly elevated in αDC1s (10–60 times) compared to sDCs. αDC1s also induced significantly higher numbers of functional CD8+ T cells against CLL cells, as determined by IFN-γ ELISPOT, using anti-MHC class I blocking mAb (W6/32) to verify the specificity of CTL responses. Our data demonstrate that αDC1s are a potent alternative to standard DCs as inducers of T cells for adoptive immunotherapy in patients with CLL and a clinical trial will be initiated.

Enhanced In Vivo activation of Adoptively Transferred Genetically Targeted T Cells Following Cyclophosphamide Chemotherapy: Initial Results From a Phase I Clinical Trial Treating CLL Patients with Autologous CD19-Targeted T Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3436-3436
Author(s):  
Renier J. Brentjens ◽  
Daniel Hollyman ◽  
Jae Park ◽  
Elmer Santos ◽  
Raymond Yeh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
High Efficiency ◽  
Conflicts Of Interest ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Autologous Tumor

Abstract Abstract 3436 Poster Board III-324 Patient T cells may be genetically modified to express chimeric antigen receptors (CARs) targeted to antigens expressed on tumor cells. We have initiated a clinical trial treating chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients with autologous T cells modified to express the 19-28z CAR targeted to the CD19 antigen expressed on most B cell malignancies. In the first cohort of this trial, patients were infused with the lowest planned dose of modified T cells alone. All patients treated in this cohort experienced low-grade fevers following modified T cell infusion, and 2 of 3 treated patients exhibited subjective and laboratory evidence of transient reductions in tumor burden. The first patient treated on the second cohort of this study received prior cyclophophamide chemotherapy followed by the same dose of modified T cells administered to the first cohort of patients. This patient experienced persistent fevers, dyspnea, hypotension, renal failure, and died 44 hours following modified T cell infusion, likely secondary to sepsis. Modified T cells were not detectable in the peripheral blood of treated patients at 1 hour following completion of T cell infusion. However, post mortem analyses revealed a rapid infiltration of targeted T cells into anatomical sites of tumor involvement. Serum levels of the inflammatory cytokines IL-5, IL-8, and GM-CSF, but not TNFα, markedly and rapidly increased following infusion of genetically targeted T cells in this patient, mirroring the in vitro cytokine secretion profile of this patient's T cells, and consistent with marked in vivo activation of the modified T cells. Similar cytokine signatures were not found in patients from the first cohort. Significantly, serum cytokine analyses from the second cohort patient revealed a marked increase in the pro-proliferative cytokines IL-2, IL-7, IL-12, and IL-15 following cyclophosphamide therapy, in contrast to the baseline levels found in the first cohort. This report demonstrates the high efficiency trafficking of CD19-targeted T cells and in vivo activation of T cells encoding a second generation CD28/zeta chain-based chimeric antigen receptor. Furthermore, these data highlight mechanisms whereby cyclophosphamide may generate an in vivo milieu that enhances the anti-tumor efficacy of autologous tumor targeted T cells. Disclosures No relevant conflicts of interest to declare.

Increased CD39 Expression on CD4+ T-Lymphocytes Has Clinical and Prognostic Significance in Chronic Lymphocytic Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3895-3895
Author(s):  
Yair Herishanu ◽  
Inbal Hazan-Hallevi ◽  
Sigi Kay ◽  
Varda Deutsch ◽  
Aaron Polliack ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Anti Inflammatory

Abstract Abstract 3895 Chronic lymphocytic leukemia (CLL) cells depend on their microenvironment for proliferation and survival. Ectonucleotidase CD39 has anti-inflammatory properties as it hydrolyzes pro-inflammatory extra-cellular ATP, generates anti-inflammatory adenosine and also protects regulatory T cells from ATP-induced cell death. In this study we investigated the clinical significance of CD39 expression on CD4+T-cells in 45 patients with CLL as well as its compartmental regulation and explored the possible mechanisms for its induction. Compared to healthy individuals, CD4+CD39+ lymphocytes were increased in the peripheral blood of patients with CLL (4.6%±2.28 vs. 17.3%±12.49, respectively, p=0.004), and correlated with advanced stage of disease (9.72%±5.76, 18.15%±12.03 and 25.90%±16.34, of CD4+ lymphocytes, in patients with Rai stages 0, 1+2 and 3+4, respectively, p=0.019). CD4+CD39+ cells were also higher in patients with CLL who needed therapeutic intervention (untreated; 12.99%±10.63 vs treated; 22.21%±12.88, p=0.01) and in those who were ZAP70+ or had b2-microglobulin levels>3g/L. There were more CD4+CD39+ lymphocytes in the bone marrow compartment (22.25%±16.16) than in the peripheral blood (16.60%±15.84, p=0.009). In-vitro studies showed that CD39 can be induced on CD4+cells by exposure to ATP or indirectly, following B-cell receptor (BCR) engagement (CD4+CD39+ lymphocytes increased by 1.56 fold, in the BCR engaged samples compared to their paired controls; 20.27%±11.3 vs. 13%±9.42, respectively, p=0.0006). Conclusions: Increased CD39 expression on CD4+ T-lymphocytes in CLL associates with an aggressive disease. This may reflect the ability of the leukemic cells to suppress the surrounding immune environment, and contribute to a poorer prognosis. CD39+ may also serve as a future target for the development of novel therapies with immune modulating anti–tumor agents in CLL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes.

1978 ◽  
Vol 148 (6) ◽  
pp. 1570-1578 ◽  
Author(s):  
S M Fu ◽  
N Chiorazzi ◽  
H G Kunkel ◽  
J P Halper ◽  
S R Harris
Keyword(s):  
T Cells ◽  
B Cells ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Pokeweed Mitogen ◽  
In Vitro Differentiation ◽  
Immunoglobulin Synthesis

Successful induction of in vitro differentiation and immunoglobulin synthesis of the leukemic lymphocytes was carried out in two cases of chronic lymphocytic leukemia. Few plasma cells and little specific Ig secretion were detected in the cultures of isolated leukemic B cells in either the presence or the absence of autologous T cells. Up to 30% of the leukemic B cells matured to plasma cells, and a 32-fold increase in specific Ig synthesis was observed when T cells from normal individuals were added to the cultures of these leukemic B cells. In one of the two cases, autologous T cells were able to induce greater than 50% of the leukemic B cells to differentiate further to plasma cells in the presence of pokeweed mitogen. This markedly accelerated in vitro differentiation was only achieved with leukemic cells from cases in which there was evidence of slight differentiation in vivo. No evidence could be obtained for excessive suppressor T cells in these patients. However, a T-cell defect in the generation of allogeneic effect helper factors was identified. This defect may be responsible for the reduced rate of leukemic maturation in vivo.

scholarly journals CD4+ T cells sustain aggressive chronic lymphocytic leukemia in Eμ-TCL1 mice through a CD40L-independent mechanism

2021 ◽  
Vol 5 (14) ◽  
pp. 2817-2828
Author(s):  
Matteo Grioni ◽  
Arianna Brevi ◽  
Elena Cattaneo ◽  
Alessandra Rovida ◽  
Jessica Bordini ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Antigen Specificity

Abstract Chronic lymphocytic leukemia (CLL) is caused by the progressive accumulation of mature CD5+ B cells in secondary lymphoid organs. In vitro data suggest that CD4+ T lymphocytes also sustain survival and proliferation of CLL clones through CD40L/CD40 interactions. In vivo data in animal models are conflicting. To clarify this clinically relevant biological issue, we generated genetically modified Eμ-TCL1 mice lacking CD4+ T cells (TCL1+/+AB0), CD40 (TCL1+/+CD40−/−), or CD8+ T cells (TCL1+/+TAP−/−), and we monitored the appearance and progression of a disease that mimics aggressive human CLL by flow cytometry and immunohistochemical analyses. Findings were confirmed by adoptive transfer of leukemic cells into mice lacking CD4+ T cells or CD40L or mice treated with antibodies depleting CD4 T cells or blocking CD40L/CD40 interactions. CLL clones did not proliferate in mice lacking or depleted of CD4+ T cells, thus confirming that CD4+ T cells are essential for CLL development. By contrast, CD8+ T cells exerted an antitumor activity, as indicated by the accelerated disease progression in TCL1+/+TAP−/− mice. Antigen specificity of CD4+ T cells was marginal for CLL development, because CLL clones efficiently proliferated in transgenic mice whose CD4 T cells had a T-cell receptor with CLL-unrelated specificities. Leukemic clones also proliferated when transferred into wild-type mice treated with monoclonal antibodies blocking CD40 or into CD40L−/− mice, and TCL1+/+CD40−/− mice developed frank CLL. Our data demonstrate that CD8+ T cells restrain CLL progression, whereas CD4+ T cells support the growth of leukemic clones in TCL1 mice through CD40-independent and apparently noncognate mechanisms.

Nicotinamide Promotes Apoptosis In Chronic Lymphocytic Leukemia through Activation of the p53/Mir-34a/SIRT1 Tumor Suppressor Network

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4627-4627
Author(s):  
Valentina Audrito ◽  
Tiziana Vaisitti ◽  
Sara Serra ◽  
Davide Rossi ◽  
Daniela Gottardi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Conflicts Of Interest ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Disease Model ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Intrinsic Resistance

Abstract Abstract 4627 Nicotinamide (Nam), is the main precursor of nicotinamide adenine dinucleotide (NAD+). It regulates intracellular levels of NAD+ and consequently activities of four classes of NAD+-consuming enzymes, including NADases, mono-ADP-ribosyl transferases (ARTs), poly-ADP-ribose polymerases (PARPs) and sirtuins. Pharmacological doses of Nam inhibit the physiological activation and proliferation of mouse B lymphocytes, suggesting that this agent might affect also human B cell homeostasis. We approaches this issue by comparing the effects of Nam on normal vs. leukemic B lymphocytes. Chronic lymphocytic leukemia (CLL) was selected as disease model, for testing in vitro the therapeutic potential of Nam, due its intrinsic resistance to apoptosis, mediated by an imbalance in the mechanisms regulating cell death, mainly regulated through the activities of NAD+-dependent enzymes. This study shows that pharmacological doses of Nam (5-10 mM) significantly inhibit proliferation and induce apoptosis of CLL cells. At earlier time points, Nam markedly reduces phosphorylation of multiple intracellular substrates, including ERK1/2. Normal B lymphocytes, used as control, were significantly less sensitive to the action of Nam. We hypothesized that these effects could be explained at least in part as a consequence of the inhibitory effects of Nam on NAD+-consuming enzymes. Attention was focused on SIRT1, a deacetylase that plays a critical role in cancer and that acts as a longevity factor. The results demonstrate that Nam exposure inhibits the activity, and also the expression of SIRT1. This effect is apparent only in leukemic cells, where SIRT1 protein levels are significantly higher than in normal B lymphocytes, obtained from spleen or tonsils, markedly less sensitive to Nam effects. The functional block of SIRT1 induced by Nam is followed by activation of p53, transcription of miR-34a and translational repression of SIRT1 mRNA (p53/miR-34a/SIRT1 functional loop). The endpoint is the activation of apoptosis. The same loop is the target of conventional DNA-damaging drugs, such as etoposide. Thus, addition of Nam to conventional DNA-damaging chemotherapeutics agents, leads to an inhibition of SIRT1 through two independent and synergic pathways, resulting in additive effects on apoptosis. In conclusion this work suggests that Nam represents a potentially useful non-chemotherapeutic agent, characterized by a known and established safety profile, to be associated to conventional cytotoxic drugs in the treatment of selected forms of CLL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4736-4745 ◽  
Author(s):  
Greta Maria Paola Giordano Attianese ◽  
Virna Marin ◽  
Valentina Hoyos ◽  
Barbara Savoldo ◽  
Irene Pizzitola ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Lymphocytes ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Car T Cells ◽  
Car T

Abstract Chronic lymphocytic leukemia (CLL) is characterized by an accumulation of mature CD19+CD5+CD20dim B lymphocytes that typically express the B-cell activation marker CD23. In the present study, we cloned and expressed in T lymphocytes a novel chimeric antigen receptor (CAR) targeting the CD23 antigen (CD23.CAR). CD23.CAR+ T cells showed specific cytotoxic activity against CD23+ tumor cell lines (average lysis 42%) and primary CD23+ CLL cells (average lysis 58%). This effect was obtained without significant toxicity against normal B lymphocytes, in contrast to CARs targeting CD19 or CD20 antigens, which are also expressed physiologically by normal B lymphocytes. Moreover, CLL-derived CD23.CAR+ T cells released inflammatory cytokines (1445-fold more TNF-β, 20-fold more TNF-α, and 4-fold more IFN-γ). IL-2 was also produced (average release 2681 pg/mL) and sustained the antigen-dependent proliferation of CD23.CAR+ T cells. Redirected T cells were also effective in vivo in a CLL Rag2−/−γc−/− xenograft mouse model. Compared with mice treated with control T cells, the infusion of CD23.CAR+ T cells resulted in a significant delay in the growth of the MEC-1 CLL cell line. These data suggest that CD23.CAR+ T cells represent a selective immunotherapy for the elimination of CD23+ leukemic cells in patients with CLL.

scholarly journals Expression of interleukin-2 receptor on T cell chronic lymphocytic leukemia cells and their response to interleukin-2

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 316-321
Author(s):  
M Tsudo ◽  
T Uchiyama ◽  
H Umadome ◽  
Y Wano ◽  
T Hori ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Activated T Cells ◽  
Cell Chronic Lymphocytic Leukemia

We analyzed peripheral blood leukemic cells from six patients with T cell chronic lymphocytic leukemia (T-CLL) with monoclonal antibodies including the anti-Tac antibody, which recognizes the receptor for interleukin 2 (IL 2). The patients were divided into two groups according to the reactivity of the monoclonal antibodies. Leukemic cells from three patients with T-CLL reacted with OKT3 and T4 but not T8, whereas those from the remaining three patients reacted with OKT3 and T8 but not T4. IL 2 receptor, which is expressed on activated T cells but not on resting T cells, was preferentially expressed on T4+ T- CLL cells. The IL 2 receptor on T4+ T-CLL cells was indistinguishable from that on normal activated T cells with respect to molecular weight and downregulation by the anti-Tac antibody. Moreover, fresh T4+ T-CLL cells, but not T8+ T-CLL cells, proliferated in response to exogenous IL 2 without prior activation, and this proliferation was inhibited by the anti-Tac antibody. These results suggest that malignant growth of T4+ T-CLL cells can be regulated by IL 2 not only in vitro but also in vivo.

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