T-cell Growth Factor Receptor Research Articles

Immune system activation associated with a naturally occurring infection in Xenopus laevis

Immune system activation correlated with a naturally occurring infection has been found in the South African clawed frog Xenopus laevis. The microorganism thought to be the cause of this infection is coccobacilloid and approximately 1 μm in diameter. Since this microorganism does not grow on conventional bacterial media and it has been observed intracellularly, it may be an obligate intracellular bacterium. It has been found in Xenopus peripheral blood and in highly vascularized organs such as the spleen and liver. Splenomegaly is the only pathology thus far described for infected frogs; infection is not associated with increased morbidity or mortality. This infection has been found in all outbred frogs examined in shipments from one South African and three separate North American vendors, and has been transmitted to animals bred and raised in our laboratory. This infection has a profound effect on the immune system of Xenopus. Significant numbers of splenocytes from infected individuals exhibit morphology commonly associated with activated T lymphocytes. There is constitutive production of T-cell growth factor (TCGF) and both IgM and IgY. Freshly harvested splenocytes from infected animals proliferate in response to a TCGF-containing supernatant, indicating that they express receptors for TCGF, a trait exclusively exhibited by activated lymphocytes. These splenocytes also show an increase in the activation marker recognized by the monoclonal antibody FJ17.

Simultaneous increased expression of E‐rosette receptor (CD2, T11) and T cell growth factor receptor on human T lymphocytes during activation

The E-rosette receptor (CD2, T11) is a differentiation antigen expressed on immature and mature human T lymphocytes. Activation of T cells from human peripheral blood with phytohemagglutinin (PHA) or with monoclonal antibody to the CD3-Ti complex (anti-Leu-4) caused the expression of CD2 to increase 10- to 20-fold. Dual parameter correlated analyses with antibody to the T cell growth factor (TCGF) receptor (anti-Tac) and anti-CD2 antibody demonstrated that the increase in CD2 expression occurred at the same time and on the same cells that expressed the TCGF receptor after stimulation with PHA. The increased expression of CD2 and the initial expression of Tac were totally inhibited by cycloheximide, but were not affected by sufficient actinomycin-D to block the T cell proliferative response. The expression of CD2 was compared with the expression of CD4 and CD8, i.e., T cell differentiation antigens on cytotoxic/suppressor or helper T cells, respectively. Although virtually all of the small percentage of freshly isolated Tac+ peripheral blood cells belonged to the CD4+, CD8- subset, both CD4+ and CD8+ T cells were equivalently activated by PHA to express Tac. By 20-30 hr after activation, the expression of CD4 or CD8 was initially decreased 10-50%. Subsequently, the expression of CD4 and CD8 returned to the levels on resting T cells but did not increase further. Therefore, the increase in CD2 expression does not reflect a universal property of cell surface antigens on activated T lymphocytes.

T-cell growth factor receptor (Tac-antigen) expression in cutaneous lymphoid infiltrates

A total of ninety-four biopsies from normal skin, benign dermatoses, and lesions of human T cell lymphotropic virus type I (HTLV-I)-positive and -negative cutaneous T cell disorders have been examined immunohistologically for reactivity with anti-Tac (monoclonal anti-T cell growth factor receptor). Tac-positive T cells were plentiful in approximately half the specimens, and they were equally frequent in benign and malignant disorders and in HTLV-I-positive and -negative cutaneous T cell disorders. Furthermore, in diseased skin, reactivity with anti-Tac was not confined to T lymphocytes, since it was also a property of dermal macrophages and Langerhans cells, as shown by examination of serial and/or double-stained sections. Comparison with other markers linked to T cell activation and proliferation (i.e., HLA-DR, OKT10 antigen, transferrin receptor, and the Ki-67 nuclear antigen) showed that Tac-antigen expression did not correlate clearly with any of these markers. These data indicate that anti-Tac forms a useful supplement to other monoclonal antibodies for the identification of activated cell subsets in cutaneous lymphoid infiltrates, but they also show that the use of this reagent on cutaneous biopsy specimens is of only limited diagnostic value.

The induction of the human T‐cell growth factor receptor precedes the production of RNA and occurs in the presence of inhibitors of RNA synthesis

The receptor for T-cell growth factor (TCGF) is an activation antigen that is present in low amounts on a small fraction of resting T lymphocytes. The TCGF receptor on human T cells can be detected with the anti-Tac monoclonal antibody within 7-12 h of stimulating the cells with phytohemagglutinin (PHA). In the current studies, we examined human lymphocytes cultured alone, with PHA, or with PHA plus sufficient actinomycin-D to inhibit RNA synthesis. After varying intervals, aliquots of the lymphocytes were stained with acridine orange (AO) or pyronin-Y(PY) to measure RNA and/or with anti-Tac plus FITC goat anti-mouse Ig. Tac expression began to increase after 6-8 h incubation with PHA, whereas increases in PY or AO staining were not detected until 12 h or later. Furthermore, the initial increase in Tac expression was not affected by sufficient actinomycin-D to block all detectable nucleic acid synthesis. Therefore, it appears that the initial expression of TCGF receptors detected after lymphocyte activation does not require de novo production of RNA.

The human receptor for T-cell growth factor. Evidence for variable post-translational processing, phosphorylation, sulfation, and the ability of precursor forms of the receptor to bind T-cell growth factor.

The T-cell growth factor (TCGF) receptor on phytohemagglutinin-activated normal peripheral blood T-cells is characterized as a glycoprotein with an apparent Mr = 55,000 that contains N-linked and O-linked carbohydrate with only approximately 33,000 daltons of peptide structure (p33) as evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There are two N-linked glycosylated intermediate precursor forms (apparent Mr = 35,000 (p35) and 37,000 (p37]. This receptor differs from the TCGF receptor on HUT-102B2 cells (apparent Mr = 50,000) because of differences in post-translational processing. Experiments with the carboxylic ionophore monensin demonstrate blockade of the transition of the p35 and p37 receptor precursor forms to the mature receptor, presumably secondary to inhibition of Golgi-associated receptor processing. We identify the primary translation product of TCGF receptor mRNA as intermediate in size between the p33 and the p35/p37 forms. We further demonstrate that the p33, p35, and p37 precursor forms, but not the primary translation product, are all capable of binding TCGF. Thus, the removal of the signal peptide and/or conformational changes of the primary translation product are necessary for ligand binding; however, the extensive post-translational modifications are not. Lastly, we demonstrate that at least some TCGF receptors are phosphorylated and sulfated, and that TCGF receptors on phytohemagglutinin-activated normal T-cells are more heavily sulfated than those on HUT-102B2 cells.

Receptors for T-cell growth factor: structure, function and expression on normal and neoplastic cells.

“During the years since its discovery (Morgan et al., 1976), the preception of T-cell growth factor (TCGF), also called Interleukin-2 (IL-2),” an in vitro novelty has given way to an appreciation of its crucial role both in the immune response and in the etiology and potential therapy of a number of diseases. In addition to playing a pivotal role in the culturing and cloning of T cells (Gillis and Smith, 1977; Schreier et al., 1980), TCGF potentiates the release of a number of other important lymphokines, including γ-interferon (γ-IFN) (Farrar et al., 1981; Kasahara et al., 1983), B-cell growth factor (BCGF) (Howard et al., 1983), and B-cell differentiation factor (BCDF) (Inaba et al., 1983). Moreover, TCGF or defects in its production or function have been implicated in such pathological states as congenital and acquired immunodeficiency (Palladino et al, 1984; Flomenberg et al, 1983; Harel-Bellan et al., 1983; Stotter et al, 1980; Thoman and Weigle, 1982), autoimmunity (Altman et al, 1981; Dauphinee et al., 1981; Linker-Israeli et al., 1983), and cancer (Gootenberg et al., 1981; Rey et al, 1983). Indeed, the receptor for this growth factor is expressed on the cells of several types of neoplasms (see Section VII), raising the question of whether its presence in such instances is fortuitous or physiologically significant. From the viewpoint of clinical therapy, several reports have appeared demonstrating the efficacy of TCGF in promoting in vitro and in vivo activity of alloreactive (Kern et al,1981) and tumor-reactive T-cells as well as natural and lymphokine-activated killer populations (Lotze et al, 1980, 1981; Wagner et al., 1980; Gillis and Watson, 1981; Cheever et al., 1982; Hefeneider et al., 1983; Eberlein et al., 1982; Rosenberg et al., 1983; Paetkau et al., 1982; Merluzzi et al., 1983; Henney et al., 1981, Donohue et al., 1984; Grimm et al., 1983).

The mechanism of cell-mediated cytotoxicity: IV. K-76 COONa, Which inhibits the activity of factor I and of C5, inhibits early events in cytotoxic T-lymphocyte-mediated cytolysis and in T-lymphocyte activation

K-76 COONa is a derivative of a fungal product which blocks complement (C)-mediated lysis by combining with C5 and preventing its activation to C5b. K-76 COONa can also combine with Factor I and inhibit its ability to hydrolyze C3b to iC3b. The inclusion of K-76 COONa at concentrations similar to those which inhibit C lysis blocked both murine cytotoxic-T-lymphocyte (CTL)-mediated lysis (CML) and the lectin-stimulated proliferative response of murine and human T lymphocytes. A modified cation pulse procedure has been used to determine which phases of CML were most sensitive to the drug. K-76 COONa was inhibitory when it was added to CML prior to the early Mg +2-dependent binding phase, but was much less effective when it was added at any time after the formation of CTL-target conjugates. The principal effect of the drug on the proliferative response was also exerted during an early phase of the response. K-76 COONa did not appreciably decrease the production of T-cell growth factor (TCGF), but it did inhibit the induction of TCGF receptor expression by both functional criteria, i.e., induction of responsiveness to TCGF, and by morphological criteria, i.e., the expression of the Tac antigen. Later events, such as the TCGF-dependent proliferation of cycling T cells, were less sensitive to the drug. Evidence is discussed suggesting that molecules similar to Factor I and to C3 may be involved both in the early events of CML and of T-lymphocyte activation.

Pseudomonas exotoxin-anti-TAC. Cell-specific immunotoxin active against cells expressing the human T cell growth factor receptor.

An immunotoxin was constructed with an activity that discriminated between two T cell lines based on the expression of the T cell growth factor (TCGF) receptor on their cell surface. A toxic protein conjugate, designated PE-anti-TAC, was made by chemically coupling pseudomonas exotoxin (PE) to a monoclonal antibody (anti-TAC) that recognizes the human TCGF receptor. This conjugate was toxic to HUT-102 cells, a cell line that expresses the TCGF receptor, but was nontoxic for MOLT-4 cells, a receptor-negative line. The toxicity of PE-anti-TAC was enhanced 50-fold in the presence of human adenovirus type II and was reduced to control levels by adding excess anti-TAC antibody. The toxicity of PE-anti-TAC for HUT-102 cells was compared with PE-anti-transferrin receptor. To compare the route of entry for both anti-TAC and anti-TFR using electron microscopy, protein conjugates were made by coupling horseradish peroxidase (HRP) to each antibody. Anti-TFR-HRP entered HUT-102 cells by concentrative adsorptive endocytosis via coated pits, and the majority of the antibodies bound to the cell surface at 4 degrees C were seen in receptosomes by 10 min after warming to 37 degrees C. Anti-TAC-HRP was also found to enter HUT-102 cells via coated pits and receptosomes; but, in contrast to anti-TFR, anti-TAC did not selectively concentrate in coated pits, and therefore the majority of this surface-bound antibody were not internalized in HUT-102 cells by 10 min at 37 degrees C.

Characterization of soluble factors that induce the cytolytic activity and the expression of T cell growth factor receptors of a T cell hybrid.

A rat X mouse T cell hybrid (PC60) proliferates in the absence of T cell growth factor (TCGF) and its cytolytic activity can be induced by culture in mixed leukocyte culture supernatants or concanavalin A-activated rat spleen cell supernatant (CS) to lyse 51Cr-labeled tumor target cells. To characterize the factor(s) responsible for this reversible induction, serum-free CS was fractionated by reverse phase high performance liquid chromatography and by phenyl-Sepharose chromatography. A cytotoxicity-inducing activity (CIA) was separated from TCGF and macrophage-activating factor/interferon-gamma. CIA was found to be a macromolecule with an apparent molecular weight of 12,000-18,000 and a pI of 5.0 and 6.2. Its activity on PC60 cells depended on the addition of TCGF. Thus TCGF may have other effects on T cells than the induction of entry into cell cycle. The number of TCGF surface receptors on PC60 cells was measured using purified 3H-TCGF. TCGF receptors were undetectable on noninduced cells but appeared during induction. The expression of TCGF receptors was not induced either by TCGF or by CIA-containing supernatants or fractions alone, only by a combination of both. These results show that TCGF plays a role in the regulation of the expression of its own receptors.

Isolation of HTLV-transformed B-lymphocyte clone from a patient with HTLV-associated adult T-cell leukaemia.

The human T-cell leukaemia/lymphoma virus (HTLV) is an exogenous retrovirus which has been associated with adult T-cell leukaemia/lymphoma (ATL). This malignancy of T lymphocytes is endemic to southern Japan, the West Indies, and to a lesser extent, the Middle East, Central Africa and the southeastern United States. ATL cells from patients of diverse geographical origins have been found to be infected with HTLV-1 (ref.6). HTLV is normally tropic for mature T lymphocytes, especially those expressing the helper-inducer surface antigen phenotype (OKT4 or Leu-3-positive), and the neoplastic T cells infected with HTLV generally express receptors for T-cell growth factor (detected by reactivity with anti-Tac antibody). However, we report here the isolation of a HTLV-infected B-lymphocyte clone from the peripheral blood of a patient with ATL. This clone is cytogenetically normal and is not infected with Epstein-Barr virus (EBV). Co-culture of cells from this clone with cord blood lymphocytes resulted in transmission of HTLV and the immortalization of either T or B lymphocytes. These results suggest that HTLV may be associated with a broader range of host cells than previously recognized.

The production of T-cell growth factor (TCGF) in vivo in sheep

Lymph and supernatants derived from efferent lymphocytes leaving the popliteal lymph nodes of sheep responding to human red cells or dinitrophenylated bovine serum albumin were examined for the presence of T-cell growth factor (TCGF). Efferent cells from normal sheep, but not from antigen-stimulated sheep, were found to release low levels of TCGF when incubated in medium for 12 hr in the absence of any exogenous stimulus. High levels of TCGF were found in normal lymph and also in immune lymph collected from sheep during the first 6 hr of immune responses. There were no detectable levels of TCGF in lymph collected later in the response. The lymphokine appeared to be a single molecular species of 10,000–20,000 molecular weight as assessed by exclusion chromatography. Efferent cells expressing receptors for TCGF were found in efferent lymph during the first 12 hr of the response. The results demonstrate for the first time that TCGF is produced in vivo and that asynchrony exists between TCGF production and expression of receptors for TCGF on efferent cells released by the stimulated node. Based on the known kinetics of previously reported synergistic factors, mitogenic factors, and T-cell-replacing factors in sheep efferent lymph and their physical characteristics it was concluded that the TCGF detected in lymph is distinct from these factors.

Deoxyadenosine (AdR) inhibition of newly activated lymphocytes: blockade at the G0-G1 interface.

The mechanism responsible for the lymphocytotoxicity associated with congenital adenosine deaminase (ADA) deficiency has been ascribed to an accumulation of dATP. Elevated levels of dATP can then lead to inhibition of DNA synthesis by inhibiting ribonucleotide reductase and causing a depletion of the other deoxynucleotide triphosphates (dNTP). This hypothesis was derived principally from studies with murine and human lymphoblastoid cell lines (LCL) and apparently confirmed in a limited number of investigations with lectin-stimulated lymphocytes. Our biochemical studies of lectin-stimulated mouse and human lymphocytes were not consistent with the dATP model and suggested that AdR exerted effects on lymphocyte activation that preceded the initiation of DNA synthesis. In the current studies, we focused on the effects of AdR on the early events in T lymphocyte activation, because we found they were the most sensitive to AdR toxicity. AdR blocked neither the production of T cell growth factor (TCGF) by lectin-stimulated lymphocytes nor the expression of TCGF receptors as detected by the anti-Tac monoclonal antibody that recognizes the human TCGF receptor. AdR did, however, block the early TCGF-dependent events leading to the entry into the cell cycle. By using the metachromatic fluorescence stain acridine orange, we found that AdR blocked the increased synthesis of RNA that characterizes the entry into the G1 phase of the cell cycle from the G0, resting state. Because these early effects were caused by the lowest doses of AdR, and because they preceded the synthesis of DNA by 15 to 20 hr, it suggested that these effects may be principally responsible for the in vivo toxicity associated with ADA deficiency. Furthermore, none of the other proposed biochemical mechanisms, e.g., inhibition of methylation, diminution of ATP levels, or incorporation of AdR into polyadenylated RNA, appeared adequate to explain AdR toxicity during T lymphocyte activation.

Characterization of the human receptor for T-cell growth factor.

Anti-Tac monoclonal antibody has been identified as a putative antibody against the receptor for T-cell growth factor (TCGF). We now show that: (i) TCGF blocks 85% of 3H-labeled anti-Tac binding to phytohemagglutinin-activated lymphoblasts and (ii) both anti-Tac and anti-TCGF immunoprecipitate a protein band that appears to represent TCGF crosslinked to its receptor on HUT-102B2 cells. In HUT-102B2 cells, the TCGF receptor is a Mr 50,000 glycoprotein with internal disulfide bond(s) and a pI of 5.5-6.0, and it represents approximately equal to 0.05% of total cellular de novo protein synthesis. It contains a peptide of Mr 33,000 that is processed to a mature form that includes N-linked and O-linked sugars and sialic acid.

Association of human T-cell leukaemia/lymphoma virus with the Tac antigen marker for the human T-cell growth factor receptor

Certain adult T-cell lymphoproliferative disorders are associated with human T-cell leukaemia virus (HTLV), a unique human type C retrovirus. (The strains of HTLV used in these studies belong to the subgroup HTLV-I.) HTLV is not an endogenous agent in man, but rather is an acquired virus with T-cell tropism. Neoplastic cells from patients infected with HTLV generally express receptors for T-cell growth factor (TCGF) (interleukin-2), and do not require prior activation with antigens or lectins to undergo TCGF-induced proliferation. Furthermore, neoplastic T-cell lines originating from such patients may constitutively produce TCGF, TCGF receptors and HTLV virions. HTLV is transmissible from cell to cell, and the infection of human T cells in vitro is associated with the expression of TCGF receptors, which can be identified by the monoclonal antibody termed anti-Tac. In our experience to date, T-cell populations that produce HTLV without exception also express epitopes found on TCGF receptors. Recognition of an association between HTLV virions and the Tac antigen would have clinical and theoretical implications. We now present evidence that during the replication or release of HTLV, the virion becomes preferentially associated with the Tac antigen.

Differentiation antigens in human T-cell activation: Evidence that anti-V H antibodies react with a membrane structure on human T Lymphocytes distinct from the antigens detected by monoclonal antibodies of the OKT and Leu series

The effect of a panel of monoclonal antibodies and heteroantibodies on T-cell proliferation in various assay systems has been examined. The antibodies tested were directed against T-cell differentiation antigens, HLA-DR antigens, and structures defined by an anti-human V H antiserum. As the test cell system highly purified subpopulations of T-cell growth factor (TCGF)-dependent T-cell lines activated either by mitogen or antigen were used. A survey of the data indicates the following: (1) Mitogenic and antigenic triggering of T lymphocytes are mediated through partly different membrane structures. (2) Antigenic stimulation by purified protein derivative (PPD) as well as polyclonal activation induced by OKT3/anti-Leu 4 monoclonal antibodies can be inhibited by heteroantibodies raised against human immunoglobulin V H fragments thus pointing to a possible connection between the antigens detected by these antisera. (3) There does not seem to be differences between the two major subpopulations of T lymphocytes (i.e., helper/inducer and suppressor/cytotoxic cells) as to how they respond to antigens or mitogens in the investigated assay systems. (4) A clear distinction was found between T blasts specific for PPD and allogeneic cells as compared to cytotoxic T cells (CTL), as the T4 and T8 antigens seem to be functionally important for antigen recognition among CTL but not for the blasts proliferating in response to PPD and allogeneic cells. (5) An inhibitory effect of OKT3/anti-Leu 4, OKIal, and anti-HLA-DR on TCGF-dependent growth was detected, possibly indicating a steric relationship between these antigens and TCGF receptors on mitogen-induced T blasts. (6) Soluble factors obtained after incubating adherent cells with OKIal and anti-HLA-DR antibodies seemed to have an inhibitory effect on overall T-cell proliferation stressing the importance of studying the T-cell activation process at different levels in these kinds of experiments. (7) The results further suggest a complexity in the build up of antigen receptors on the various T-effector cells, perhaps also involving receptors for growth factors, HLA-DR antigens, and receptors for the latter.

Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus.

Several isolates of human T-cell leukemia/lymphoma virus (HTLV) were transmitted to normal human T cells obtained from the umbilical cord blood of newborns. T cells from seven specimens were immortalized by infection with different HTLV isolates and their properties were compared with those of activated uninfected normal T cells grown in the presence of T-cell growth factor (TCGF) and with those of HTLV-positive neoplastic T-cell lines derived from patients with T-cell malignancies. The HTLV-infected cells generally belonged to a class of mature T cells (OKT4+ and Leu 3A+) and differed from the normal uninfected cells in that they could be propagated in culture indefinitely; possessed altered morphology, including convoluted nuclei and some bi- and multinucleated giant cells; formed large clumps in culture; demonstrated a diminished requirement for TCGF; had an increased density of TCGF receptors; often became completely independent of exogenous TCGF; and expressed HLA-DR determinants. These properties of the HTLV-infected cord blood T cells contrasted to those of uncultured cord blood T cells and of cord blood cells stimulated with mitogen and grown with TCGF but resembled the characteristics of T-cell lines established previously from patients with HTLV-associated T-cell malignancies. This in vitro system offers a unique opportunity to study the basic mechanism involved in abnormal growth and neoplastic transformation of a specific class of human T cells.

T-cell growth factor receptor in adult T-cell leukemia [letter

T-cell growth factor receptor in adult T-cell leukemia [letter

Cyclosporin A does not prevent expression of Tac antigen, a probable TCGF receptor molecule, on mitogen-stimulated human T cells.

Results of recent studies indicated that a monoclonal anti-Tac antibody might recognize the receptor sites or closely related structures for T cell growth factor (TCGF) on activated human T cells. In the present study, we examined the effect of cyclosporin A (CsA) on the expression of Tac antigen by mitogen-stimulated T cells. CsA inhibited the proliferative response of T cells to Con A and PHA in a dose-dependent manner. Both Con A- and PHA-induced cellular proliferation were decreased to about 10% of controls at 5 micrograms/ml of CsA. When T cells were stimulated with these mitogens, many of them expressed Tac antigen on their surfaces, assessed by the immunoperoxidase method. The appearance of Tac-positive cells occurred earlier than a rise of cellular DNA synthesis. Characteristically, CsA showed no inhibitory effect on the expression of Tac antigen by mitogen-stimulated T cells, even at a relatively high concentration of 5 micrograms/ml, whereas the expression of other "activation" antigens reactive with monoclonal anti-Ia, OKT9, or OKT10 antibodies by T cells was blocked completely by CsA. Morphologically, the majority of Tac-positive cells in culture with mitogens alone showed the characteristics of blastoid cells; Tac-positive cells in the culture containing CsA mainly consisted of medium-sized cells, indicating these cells probably accumulated at a stage of partial activation. T cells, once stimulated with Con A or PHA for 3 days whether in the presence or in the absence of CsA, were able to absorb TCGF activity from TCGF-containing media similarly. In addition, T cells, even stimulated in the presence of CsA with these mitogens for 24 hr, were capable of responding to TCGF with the same grade of proliferation as did T cells stimulated with mitogen alone. CsA showed no appreciable inhibition in a TCGF-dependent proliferation of such prestimulated cells. These functional properties of activated T cells might be correlated with their ability to express Tac antigen. These experimental findings present some evidence that CsA might not prevent the expression of probable functional receptor sites for TCGF in mitogen-dependent activation of human T cells.

Failure of Regulation of Tac Antigen/TCGF Receptor on Adult T-Cell Leukemia Cells by Anti-Tac Monoclonal Antibody

Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down-regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.

Failure of regulation of Tac antigen/TCGF receptor on adult T-cell leukemia cells by anti-Tac monoclonal antibody

Anti-Tac monoclonal antibody, which blocks the membrane binding and action of human T-cell growth factor (TCGF), is strongly proposed to recognize TCGF receptor. We have demonstrated that anti-Tac antibody reacted with leukemic cells from patients with adult T-cell leukemia (ATL) and reacted with T-cell lines established from ATL cells. Although antigenic modulation, or down-regulation, of Tac antigen on activated normal T cells was induced by anti-Tac antibody, the expression of Tac antigen on ATL cells or T-cell lines was not affected when examined by the fluorescence-activated cell sorter (FACS) and the radioassay using 125I-staphylococcal protein A. These results indicate that regulation of Tac antigen-TCGF receptor is different between normal and malignant T cells, suggesting that failure of down- regulation of Tac antigen on leukemic cells by anti-Tac antibody may play an important role in the malignant proliferation of ATL cells.