scholarly journals A monoclonal antibody detecting a novel antigen expressed in the HTLV-I- infected cells

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 430-436 ◽  
Author(s):  
F Tsubai ◽  
Y Namba ◽  
M Kohno ◽  
S Hanada ◽  
M Matsumoto ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Cell Lines ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell

Abstract A monoclonal antibody, FTF 148, was prepared by hybridizing murine myelomal cells (NS-1) and spleen cells of BALB/c mice immunized with cultured cells derived from an adult T cell leukemia (ATL) patient (KUT- 2 cells). This monoclonal antibody reacted with all of the human T cell leukemia virus I (HTLV-I)-infected cell lines tested but did not react with other T cell lines derived from acute lymphocytic leukemia, Epstein-Barr virus-transformed B cell lines, or an erythroleukemic cell line. This monoclonal antibody was not directed to viral antigens because it reacted equally well with almost all KUT-2 and MT-1 cells, only 1% to 3% of which were ATL-associated antigen-positive. In contrast to interleukin 2 receptors expressed on both ATL cells and normal phytohemagglutinin-stimulated blasts, this antigen was not expressed on the latter cells. The antigen, mainly expressed on the cell membrane, was analyzed by metabolic labeling with 3H-leucine and surface labeling with 125I followed by cell lysis and immunoprecipitation with the FTF 148 antibody. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that p50 and p74 proteins were specifically precipitated and the antigen was also different from the product of the Xs gene of HTLV-I.

scholarly journals A monoclonal antibody detecting a novel antigen expressed in the HTLV-I- infected cells

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 430-436
Author(s):  
F Tsubai ◽  
Y Namba ◽  
M Kohno ◽  
S Hanada ◽  
M Matsumoto ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Cell Lines ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell

A monoclonal antibody, FTF 148, was prepared by hybridizing murine myelomal cells (NS-1) and spleen cells of BALB/c mice immunized with cultured cells derived from an adult T cell leukemia (ATL) patient (KUT- 2 cells). This monoclonal antibody reacted with all of the human T cell leukemia virus I (HTLV-I)-infected cell lines tested but did not react with other T cell lines derived from acute lymphocytic leukemia, Epstein-Barr virus-transformed B cell lines, or an erythroleukemic cell line. This monoclonal antibody was not directed to viral antigens because it reacted equally well with almost all KUT-2 and MT-1 cells, only 1% to 3% of which were ATL-associated antigen-positive. In contrast to interleukin 2 receptors expressed on both ATL cells and normal phytohemagglutinin-stimulated blasts, this antigen was not expressed on the latter cells. The antigen, mainly expressed on the cell membrane, was analyzed by metabolic labeling with 3H-leucine and surface labeling with 125I followed by cell lysis and immunoprecipitation with the FTF 148 antibody. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that p50 and p74 proteins were specifically precipitated and the antigen was also different from the product of the Xs gene of HTLV-I.

scholarly journals Rat lymphoid cell lines producing human T cell leukemia virus. II. Constitutive expression of rat interleukin 2 receptor.

1985 ◽  
Vol 161 (5) ◽  
pp. 924-934 ◽  
Author(s):  
J Yodoi ◽  
M Okada ◽  
Y Tagaya ◽  
K Teshigawara ◽  
K Fukui ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Lymphoid Cell ◽  
Interleukin 2 ◽  
Constitutive Expression ◽  
Receptor Expression ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Lymphoid Cell Lines

Three rat lymphoid cell lines (TARS-1, TARL-2, and TART-1) (12) transformed by human T cell leukemia/lymphoma virus I (HTLV-I) had rearrangement of the beta chain gene of the T cell antigen receptor, and had integrated proviral DNA from HTLV-I in their genomes. As is the case with adult T cell leukemia (ATL)-derived human T cell lines transformed by HTLV-I, these rat cell lines unequivocally expressed interleukin 2 (IL-2) receptor, as determined by radiolabeled IL-2 binding. By Scatchard plot analysis, one of the cell lines, TART-1, proved to have high affinity receptors (Ka = 1.3 X 10(11)/M and 8.8 X 10(9)/M). Rat IL-2 receptor, not human IL-2 receptor, was expressed on HTLV+ rat cell lines, as demonstrated by the fact that they expressed antigens reactive with monoclonal antibodies (ART-18) against rat IL-2 receptor, but not with anti-Tac antibodies. The collective evidence indicates that the endogenous IL-2 receptor gene is activated in human and rat lymphoid cell lines with HTLV-I production. The mechanism of abnormal IL-2 receptor expression in HTLV infection is discussed.

scholarly journals The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1701-1712 ◽  
Author(s):  
TA Waldmann ◽  
JD White ◽  
CK Goldman ◽  
L Top ◽  
A Grant ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Rational Approach ◽  
Resting Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotrophic virus-I (HTLV-I). It is an aggressive leukemia with an overall mortality rate of 50% within 5 months; no conventional chemotherapy regimen appears successful in inducing long-term disease-free survival in ATL patients. However, ATL cells constitutively express high-affinity interleukin-2 receptors (IL-2Rs) identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference in receptor expression, we administered anti-Tac intravenously (IV) to 19 patients with ATL. In general the patients did not suffer untoward reactions, and in 18 of 19 cases did not have a reduction in normal formed elements of the blood. Seven patients developed remissions that were mixed (1 patient), partial (4 patients), or complete (2 patients), with partial and complete remissions lasting from 9 weeks to more than 3 years as assessed by routine hematologic tests, immunofluorescence analysis, and molecular genetic analysis of T-cell receptor gene rearrangements and of HTLV-I proviral integration. Furthermore, remission was associated with a return to normal serum calcium levels and an improvement of liver function tests. Remission was also associated in some cases with an amelioration of the profound immunodeficiency state that characterizes ATL. Thus the use of a monoclonal antibody that blocks the interaction of IL-2 with its receptor expressed on ATL cells provides a rational approach for treatment of this aggressive malignancy.

scholarly journals Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1805-1816 ◽  
Author(s):  
TA Waldmann ◽  
CK Goldman ◽  
KF Bongiovanni ◽  
SO Sharrow ◽  
MP Davey ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Interleukin 2 ◽  
Rational Approach ◽  
Resting Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Antitumor Effects ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.

scholarly journals The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia

Blood ◽  
1993 ◽  
Vol 82 (6) ◽  
pp. 1701-1712 ◽  
Author(s):  
TA Waldmann ◽  
JD White ◽  
CK Goldman ◽  
L Top ◽  
A Grant ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Rational Approach ◽  
Resting Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotrophic virus-I (HTLV-I). It is an aggressive leukemia with an overall mortality rate of 50% within 5 months; no conventional chemotherapy regimen appears successful in inducing long-term disease-free survival in ATL patients. However, ATL cells constitutively express high-affinity interleukin-2 receptors (IL-2Rs) identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference in receptor expression, we administered anti-Tac intravenously (IV) to 19 patients with ATL. In general the patients did not suffer untoward reactions, and in 18 of 19 cases did not have a reduction in normal formed elements of the blood. Seven patients developed remissions that were mixed (1 patient), partial (4 patients), or complete (2 patients), with partial and complete remissions lasting from 9 weeks to more than 3 years as assessed by routine hematologic tests, immunofluorescence analysis, and molecular genetic analysis of T-cell receptor gene rearrangements and of HTLV-I proviral integration. Furthermore, remission was associated with a return to normal serum calcium levels and an improvement of liver function tests. Remission was also associated in some cases with an amelioration of the profound immunodeficiency state that characterizes ATL. Thus the use of a monoclonal antibody that blocks the interaction of IL-2 with its receptor expressed on ATL cells provides a rational approach for treatment of this aggressive malignancy.

scholarly journals Interleukin 2 inhibits in vitro growth of human T cell lines carrying retrovirus.

1985 ◽  
Vol 161 (5) ◽  
pp. 1243-1248 ◽  
Author(s):  
K Sugamura ◽  
S Nakai ◽  
M Fujii ◽  
Y Hinuma
Keyword(s):  
T Cell ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Specific Binding ◽  
Interleukin 2 ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
T Cell Lines

Four human T cell lines, TL-Mor, TL-Su, TL-TerI, and TL-OmI, carrying human T cell leukemia virus (HTLV), were established previously. TL-Mor, TL-Su, and TL-TerI were derived from interleukin 2 (IL-2)-dependent parental cell lines cloned from peripheral blood leukocytes (PBL) of three healthy HTLV carriers, while TL-OmI was directly established from PBL of a patient with adult T cell leukemia. These four TL cell lines grow autonomously without IL-2. When they were cultured in the presence of IL-2, their growth was inhibited after a few days. This growth inhibition depended on the dose of IL-2, and the effective dose significantly promoted growth of their parental IL-2-dependent cell lines. The growth inhibition is demonstrated to be due to specific binding of IL-2 to receptors on the TL cells.

DNA methylation and expression of HLA-DR alpha

1984 ◽  
Vol 4 (5) ◽  
pp. 890-897
Author(s):  
M S Reitz ◽  
D L Mann ◽  
M Eiden ◽  
C D Trainor ◽  
M F Clarke
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Dna Sequences ◽  
Antigen Expression ◽  
Lymphocytic Leukemia ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Hla Dr

B-cell lines established from two individuals with T-cell acute lymphocytic leukemia (T-ALL) express HLA-DR antigens, whereas the isogenic T-cells do not. The lack of expression correlates with a lack of detectable HLA-DR mRNA. All of the DR alpha DNA sequences detected by a cloned DR alpha cDNA probe are contained in a BglII fragment which varies slightly in size (4.0 to 4.8 kilobases) from one individual to another. In DNA from the T-cells not expressing DR alpha mRNA, all of the potential HpaII sites within the BglII fragment appeared to be methylated. In contrast, at least some of these sites were not methylated in DNA from the B-cells expressing high levels of DR alpha mRNA. Treatment of these T-cells with 5-azacytidine resulted in the induction of DR surface antigen expression, the appearance of DR alpha mRNA, and the partial demethylation of the DR alpha DNA sequences. T-cell lines established from human T-cell leukemia-lymphoma virus associated T-cell neoplasias, in contrast to the T-cell acute lymphocytic leukemia cell lines, expressed both DR antigens and DR alpha mRNA; the HpaII sites within the BglII fragment of DR alpha DNA of these human T-cell leukemia-lymphoma virus-positive T-cell lines were in all cases at least partially unmethylated. Uncultured peripheral blood T-cells from human T-cell leukemia-lymphoma virus-infected individuals expressed DR antigens at a low level, and the DR alpha locus was partially unmethylated. After 48 h in culture, DR antigen expression was substantially increased, but no significant changes were observed in methylation of the DR alpha locus or in the amount of DR mRNA which was present. This suggests that expression of DR antigens also can be modulated post-transcriptionally.

scholarly journals Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1805-1816 ◽  
Author(s):  
TA Waldmann ◽  
CK Goldman ◽  
KF Bongiovanni ◽  
SO Sharrow ◽  
MP Davey ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Interleukin 2 ◽  
Rational Approach ◽  
Resting Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Antitumor Effects ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.

scholarly journals DNA methylation and expression of HLA-DR alpha.

1984 ◽  
Vol 4 (5) ◽  
pp. 890-897 ◽  
Author(s):  
M S Reitz ◽  
D L Mann ◽  
M Eiden ◽  
C D Trainor ◽  
M F Clarke
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Dna Sequences ◽  
Antigen Expression ◽  
Lymphocytic Leukemia ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Hla Dr

B-cell lines established from two individuals with T-cell acute lymphocytic leukemia (T-ALL) express HLA-DR antigens, whereas the isogenic T-cells do not. The lack of expression correlates with a lack of detectable HLA-DR mRNA. All of the DR alpha DNA sequences detected by a cloned DR alpha cDNA probe are contained in a BglII fragment which varies slightly in size (4.0 to 4.8 kilobases) from one individual to another. In DNA from the T-cells not expressing DR alpha mRNA, all of the potential HpaII sites within the BglII fragment appeared to be methylated. In contrast, at least some of these sites were not methylated in DNA from the B-cells expressing high levels of DR alpha mRNA. Treatment of these T-cells with 5-azacytidine resulted in the induction of DR surface antigen expression, the appearance of DR alpha mRNA, and the partial demethylation of the DR alpha DNA sequences. T-cell lines established from human T-cell leukemia-lymphoma virus associated T-cell neoplasias, in contrast to the T-cell acute lymphocytic leukemia cell lines, expressed both DR antigens and DR alpha mRNA; the HpaII sites within the BglII fragment of DR alpha DNA of these human T-cell leukemia-lymphoma virus-positive T-cell lines were in all cases at least partially unmethylated. Uncultured peripheral blood T-cells from human T-cell leukemia-lymphoma virus-infected individuals expressed DR antigens at a low level, and the DR alpha locus was partially unmethylated. After 48 h in culture, DR antigen expression was substantially increased, but no significant changes were observed in methylation of the DR alpha locus or in the amount of DR mRNA which was present. This suggests that expression of DR antigens also can be modulated post-transcriptionally.

Sign in / Sign up

Export Citation Format

Share Document