scholarly journals U1B3.3 monoclonal antibody recognizes a precursor of NK1.1+ cytotoxic T cells generated by interleukin-2

2002 ◽  
Vol 78 (4) ◽  
pp. 91-95
Author(s):  
Yoshinori IKARASHI ◽  
Kazunori KATO ◽  
Mitsuzi YOSHIDA ◽  
Hiro WAKASUGI
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Cytotoxic T Cells ◽  
Interleukin 2

scholarly journals G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2826-2834
Author(s):  
PM Anderson ◽  
W Crist ◽  
D Hasz ◽  
AJ Carroll ◽  
DE Myers ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Multiparameter Flow Cytometry ◽  
Specific Lysis

A highly purified, 300-Kd bispecific monoclonal antibody (MoAb) heteroconjugate was prepared by covalently linking the anti-CD3 MoAb, G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19 heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11) acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly isolated primary bone marrow blasts from nine newly diagnosed ALL patients with a t(4;11)(q21;q23) chromosomal translocation were studied with 51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19 MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells by interleukin-2- activated CD3+ peripheral blood T-cell (PBTC) effectors but did not augment the cytolytic activity of the same effectors against CD19- T- ALL cells. In contrast to the alpha CD3 x alpha CD19 heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19 heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type- specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate. To our knowledge, this is the first description of an effective bispecific antibody that facilitates the T-cell- mediated lysis of t(4;11) ALL blasts.

scholarly journals G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2826-2834 ◽  
Author(s):  
PM Anderson ◽  
W Crist ◽  
D Hasz ◽  
AJ Carroll ◽  
DE Myers ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Multiparameter Flow Cytometry ◽  
Specific Lysis

Abstract A highly purified, 300-Kd bispecific monoclonal antibody (MoAb) heteroconjugate was prepared by covalently linking the anti-CD3 MoAb, G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19 heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11) acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly isolated primary bone marrow blasts from nine newly diagnosed ALL patients with a t(4;11)(q21;q23) chromosomal translocation were studied with 51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19 MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells by interleukin-2- activated CD3+ peripheral blood T-cell (PBTC) effectors but did not augment the cytolytic activity of the same effectors against CD19- T- ALL cells. In contrast to the alpha CD3 x alpha CD19 heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19 heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type- specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate. To our knowledge, this is the first description of an effective bispecific antibody that facilitates the T-cell- mediated lysis of t(4;11) ALL blasts.

scholarly journals CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help.

1993 ◽  
Vol 177 (6) ◽  
pp. 1791-1796 ◽  
Author(s):  
F A Harding ◽  
J P Allison
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Histocompatibility Complex ◽  
Necessary And Sufficient ◽  
Additional Antigen

The activation requirements for the generation of CD8+ cytotoxic T cells (CTL) are poorly understood. Here we demonstrate that in the absence of exogenous help, a CD28-B7 interaction is necessary and sufficient for generation of class I major histocompatibility complex-specific CTL. Costimulation is required only during the inductive phase of the response, and not during the effector phase. Transfection of the CD28 counter receptor, B7, into nonstimulatory P815 cells confers the ability to elicit P815-specific CTL, and this response can be inhibited by anti-CD28 Fab or by the chimeric B7-binding protein CTLA4Ig. Anti-CD28 monoclonal antibody (mAb) can provide a costimulatory signal to CD8+ T cells when the costimulatory capacity of splenic stimulators is destroyed by chemical fixation. CD28-mediated signaling provokes the release of interleukin 2 (IL-2) from the CD8+ CTL precursors, as anti-CD28 mAb could be substituted for by the addition of IL-2, and an anti-IL-2 mAb can block the generation of anti-CD28-induced CTL. CD4+ cells are not involved in the costimulatory response in the systems examined. We conclude that CD8+ T cell activation requires two signals: an antigen-specific signal mediated by the T cell receptor, and an additional antigen nonspecific signal provided via a CD28-B7 interaction.

scholarly journals Production and regulation of interleukin-2 in human lymphoblastic leukemias studied with T-cell monoclonal antibodies

Blood ◽  
1983 ◽  
Vol 61 (4) ◽  
pp. 781-789 ◽  
Author(s):  
S Venuta ◽  
R Mertelsmann ◽  
K Welte ◽  
SP Feldman ◽  
CY Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Gel Filtration ◽  
Lymphatic Leukemia ◽  
Daudi Cells ◽  
Self Replication

Abstract Human leukemias are illnesses of hemopoietic stem cells that go through processes of self-replication and partial differentiation under the control of as yet largely unknown growth and differentiation factors. IL-2 is a powerful factor controlling proliferation of normal T cells. We report that acute lymphoblastic leukemias of T and non-B, non-T phenotypes produce a growth factor after mitogen stimulation. This factor is able to support the proliferation of human and murine IL-2- dependent cytotoxic cells, has a mol wt of 26,000 daltons by gel filtration, an isoelectric point of 6.6, and its biologic activity is inhibited by an anti IL-2 monoclonal antibody. This factor is, therefore, by all parameters studied very similar to IL-2 produced by normal lymphocytes. A recently developed monoclonal antibody, Pan T2, binds to normal T cells, renders T cells responsive to IL-2, and induces the release of IL-2, which in turn provides the second signal for T-cell proliferation. Mononuclear cells from acute lymphoblastic leukemia do not respond to the addition of this monoclonal antibody unless cocultured with irradiated Daudi cells. Since normal T cells do not require Daudi to produce IL-2 and since Daudi cells do not produce IL-2 under any conditions, we conclude that the cell responsible for IL- 2 production in acute lymphatic leukemia is a leukemic T cell with an altered mechanism of IL-2 production at the level of the Pan T2 binding site.

Monoclonal antibody to Lyt 2 antigen blocks H–2I- and H–2K- specific mouse cytotoxic T cells

Nature ◽  
1982 ◽  
Vol 296 (5852) ◽  
pp. 76-78 ◽  
Author(s):  
Richard A. Miller ◽  
Osias Stutman
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Cytotoxic T Cells

Microheterogeneity in HLA-B35 alleles influences peptide-dependent allorecognition by cytotoxic T cells but not binding of a peptide-restricted monoclonal antibody

1993 ◽  
Vol 38 (4) ◽  
pp. 261-269 ◽  
Author(s):  
Alexander Steinle ◽  
Carsten Reinhardt ◽  
Elfriede Nöβner ◽  
Barbara Uchanska-Ziegler ◽  
Andreas Ziegler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Cytotoxic T Cells

scholarly journals Interleukin-2 Family Members and their Role in Demyelinating Disease

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
: Mahendra K Bhopale
Keyword(s):  
T Cells ◽  
Demyelinating Disease ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Th2 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Memory Cd8 T Cells ◽  
Regulatory Effects ◽  
Negative Regulatory Role

Interleukin-2 (IL-2) has a family which includes IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 cytokines. This family group of an IL-2 cytokine plays important, but different roles in neurologically related demyelinating disease studied in multiple sclerosis (MS) and it’s experimentally induced rodent models. IL-2 play role in strong T-cell expansion and participates in the maintenance of T-regs cells, but also keep in the stimulation and proliferation of pathogenic T cells. IL-4 induces differentiation of naïve helper T cells (Th0) to Th2 cells. IL-7 promotes Th1 cell differentiation. IL-9 is a hematopoietic growth factor for major pathogenic Th17 cells in EAE. IL-15 is necessary for memory CD8+ T cells and plays a negative regulatory role through CD8+ CD122+ T cells in reducing Th17-mediated inflammation. IL-21 has potent regulatory effects on the natural killer (NK) cells and cytotoxic T cells. IL-21 activates CD4+ and up-regulates the Th2 and Th17 subsets of T helper cells. Based on different roles of each family member in demyelinating disease, bio-agents and therapeutic agents have been attempted in an experimental model to study their role in demyelinating disease is described in the present review.

scholarly journals A monoclonal antibody (8H3) that binds to rat T lineage cells and augments in vitro proliferative responses.

1990 ◽  
Vol 172 (5) ◽  
pp. 1315-1323 ◽  
Author(s):  
Y Torimoto ◽  
M Kinebuchi ◽  
A Matsuura ◽  
K Kikuchi ◽  
T Uede
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Cell Surface ◽  
Surface Antigen ◽  
Interleukin 2 ◽  
Cell Surface Antigen ◽  
Double Negative ◽  
Mouse Immunoglobulin ◽  
A Cell

A murine monoclonal antibody, designated 8H3, recognizes a cell surface antigen expressed exclusively on rat T lineage cells. 8H3 antibody immunoprecipitated 180-, 120-, and 90-kD components from rat thymocytes as well as splenic T cells under nonreducing conditions. 8H3 antibody specifically inhibited the binding of thymocytes to fibronectin. Furthermore, binding of rat thymocytes to immobilized synthetic peptide Gly-Arg-Gly-Asp-Ser-Pro-Cys-BSA was inhibited by 8H3 antibody as was Gly-Arg-Gly-Asp-Ser-Pro-Cys, but not by Gly-Arg-Ala-Asp-Ser-Pro-Lys or Gly-Arg-Gly-Glu-Ser-Pro. Crosslinking of 8H3 antigen on double-negative thymocytes and adult thymocytes, as well as splenic T lymphocytes by 8H3 antibody and F(ab')2 fragments of goat antibodies to mouse immunoglobulin, led to an increase in the concentration of cytoplasmic free Ca2+ due to the release of Ca2+ from intracellular stores as well as the influx of Ca2+ from extracellular sources. Expression of interleukin 2 receptor and subsequently cell proliferation was observed upon incubation of thymocytes and splenic T cells with 8H3 antibody. Furthermore, 8H3 antibody induced the proliferation of double-negative thymocytes. These data collectively indicated that a cell surface antigen, 8H3, is involved in not only cell adhesion but also involved in the expression of immature as well as mature thymocytes.

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