PubMed Health⌕ Search

Biomedical subjects

M Allouche

Publications and source records attributed to M Allouche.

At least 19 recordsLinked to original sources
PubMed1992

Abnormal expression of IL-2R beta (p70)-binding polypeptide on HIV-infected patients' cells.

The constitutively expressed IL-2R beta (p70) chain participates in the formation of high-affinity (h.a.) IL-2R and transduces IL-2-mediated signals to normal cells. Its expression on HIV-infected patients' PBMC was evaluated and was found to be decreased in both nonstimulated CD4+ and CD8+ cells. Mitogenic cell stimulation induced IL-2R beta chain expression on both CD4+ and CD8+ cells from asymptomatic and persistent generalized lymphadenopathy patients but not on those from AIDS patients. Comparison of mean fluorescence intensity of IL-2R beta positively stained cells from normals and patients did not reveal significant differences. Cross-linking of 125I-rIL-2 on patients' PHA-blasts revealed decreased signals corresponding to both IL-2-binding chains and, in some cases, neither IL-2R alpha nor IL-2R beta chains could be detected. Decreased expression of IL-2R beta polypeptide was associated with impaired accumulation of the corresponding mRNA transcripts. Binding experiments with 125I-rIL-2 under h.a. conditions showed a decreased number of IL-2-binding sites/cell which was more pronounced in patients with AIDS than in patients with less advanced clinical stages. In vitro HIV infection of normal PHA-blasts also resulted in a decreased number of h.a. IL-2R/cell. High concentrations of rIL-2 in the absence of other mitogenic stimuli induced a decreased cell proliferation and expression of the IL-2R alpha chain and did not enhance the constitutive NK and the generation of LAK activity in several patients, suggesting an impaired IL-2R beta chain-mediated cell activation.

Antibodies, Monoclonal↗
PubMed1992

Interleukin 2 production and interleukin 2 receptor expression by human immature leukemic T cells.

In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti-IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells.

Antigens, CD↗
PubMed1992

Phorbol myristate acetate-induced expression of high-affinity interleukin 2 receptors and production of interleukin 2 by human acute lymphoblastic leukemia T cells.

The effect of phorbol myristate acetate (PMA) on the expression of interleukin 2 receptors (IL-2R), production of IL-2 and IL-2-dependent proliferation of acute lymphoblastic leukemia T cells (T-ALL cells) from 10 patients was studied. First, the effect of PMA on the expression of cell surface markers was assessed: a decrease of CD3 and CD4, and an enhanced expression of CD8 molecule were observed on T-ALL cells. Moreover, PMA exhibited an heterogenous effect on various activation-associated molecules such as a decreased expression of transferrin receptor and T10 molecule and an induced expression of 4F2 and CD9 molecules. It is known that functional high-affinity IL-2R are composed of at least two IL2 binding molecules, the alpha (p55) and beta (p70) chains. We found that PMA induced the expression of both IL-2R alpha and IL-2R beta chains, as well as IL-2 production by T-ALL cells. These effects were time- and dose-dependent. Cross-linking experiments with 125I-labelled recombinant IL-2 (125I-rIL-2) revealed both p55 (IL-R alpha) and p70 (IL-2R beta) IL-2-binding polypeptides, whereas binding equilibrium assays on PMA-treated cells demonstrated the presence of a low number (31-413) of high-affinity binding sites/cell in five out of six cases analysed, as well as intermediate affinity IL-2R (1234-3919 sites/cell) in four out of six cases, according to the time of incubation with PMA. In two cases tested high-affinity IL-2R on PMA-treated T-ALL cells could internalize 125I-rIL-2 at 37 degrees C. PMA alone enhanced the spontaneous proliferation of T-ALL cells in three cases, whereas a clear synergy between IL-2 and PMA could be detected in three patients' cells. Moreover, exogenous rIL-2 enhanced cell proliferation of PMA-preincubated T-ALL cells in four cases studied. Taken together, these observations indicate that a short-term incubation of T-ALL cells with PMA can activate the IL-2/IL-2R system on these cells without inducing strong modifications of their differentiation status. These results thus suggest that this system may be involved in the proliferation process of some activated immature T cells.

Cell Division↗
PubMed1990

Autocrine growth of leukemic cells.

Autocrine growth is a process whereby a cell both secretes and responds to a growth factor. This paper describes the stepwise malignant progression of leukemic cells which has been demonstrated in many experimental models of autocrine leukemic growth. In contrast, autocrine growth has not been proven as a major physiopathological mechanism for the growth of leukemic cells in vivo in human myeloid and lymphocytic leukemias. Growth-factor independency of human leukemic cell lines may be due to clonal selection.

Cell Division↗
PubMed1990

The role of growth-factor receptors (excluding IL-2 receptors) in the proliferation and differentiation of normal and leukemic hematopoietic cells.

Receptors (R) are considered as allosteric enzymes whose action on metabolic chains is modulated through binding to the ligand. They play an essential role in the transduction of the multiple signals (e.g. interleukins or CSF) which intervene in the regulation of hematopoiesis. Their ordered interactions are necessary to regulate the growth and differentiation of normal hematopoietic precursors. This paper summarizes recent data concerning the structure-action relationship of growth-factor receptors in the signal transduction and alterations of growth-factor receptors which may play an important role in leukemic transformation. Some therapeutic modulations of growth-factors cascades are also discussed.

Cell Differentiation↗
PubMed1990

Interleukin 2 receptors.

Interleukin 2 receptors (IL-2-R) are composed of (at least) two chains: the alpha chain (or p55 or Tac) and the beta chain (or p70 or p75). The association of both chains constitutes high affinity IL2-R complexes (Kd congruent to 10-100 pM), whereas the alpha-chain or the beta chain alone bind IL-2 with low (Kd congruent to 5-50 nM) and intermediate (Kd congruent to 1 nM) affinities, respectively. The beta chain (but not the alpha chain) mediates IL-2 internalization and signal transduction (proliferation or differentiation) to the cell, thus only high and intermediate affinity IL-2-R are functional. High affinity IL-2-R are expressed on activated normal and leukemic T and B lymphoid cells. Low affinity IL-2-R (Tac alone) are seen on stimulated T cells, B cells, and monocytes, as well as on various leukemic cells. The p70 chain alone is constitutively expressed by subsets of normal resting T and B cells, LGL and NK cells and we have recently demonstrated its presence on leukemic cells from various hemopoietic lineages. The finding of IL-2-R on non-lymphoid cells may disclose new functions for IL-2.

B-Lymphocytes↗
PubMed1990

Phorbol myristate acetate induces both high affinity and low affinity interleukin 2-receptors on a pre-B leukemic cell line.

The human pre-B leukemic cell line Reh6 does not constitutively express the Tac molecule (p55), which is one of the two polypeptide chains of the interleukin 2-receptor (IL2-R). Cell incubation with Phorbol Myristate Acetate (PMA) induces expression of the Tac molecule in a dose and time-dependent manner. Binding experiments with radiolabelled recombinant IL2 (rIL2) revealed both high and low affinity IL2-R (225 +/- 105 sites/cell with a Kd of 130 +/- 51 pM and 24060 sites/cell with a Kd of 17.3 nM respectively), whereas unstimulated Reh6 cells only expressed intermediate affinity Reh6 cells revealed the presence of two polypeptide chains of mol. wts 55,000 (Tac molecule) and 70,000, as in normal activated T cells, while the 70,000 mol. wt chain alone was observed in unstimulated Reh6 cells. IL2-R-bearing Reh6 cells could absorb rIL2 in a dose-dependent manner and this absorption was inhibited by a monoclonal antibody against the Tac molecule (anti-Tac). Moreover, partial internalization of IL2 bound under high affinity conditions occurred at 37 degrees C. IL2-R expressed on PMA-induced cells were functional since rIL2 specifically enhanced the proliferation in vitro of PMA-treated cells in semi-solid but not liquid cultures. These findings thus demonstrate an IL2-dependent mechanism of proliferation in vitro of pre-B leukemic cells induced by PMA, which can express high affinity, functional IL2-R.

Cell Division↗
PubMed1990

Effect of phorbol myristate acetate on T cell colony formation, interleukin-2 (IL-2) receptor expression and IL-2 production by cells from patients at all stages of HIV infection.

We and others have shown that several T cell responses induced by the mitogen phytohaemagglutinin (PHA), including T cell colony formation, IL-2 receptor (IL-2R) expression, and IL-2 production are impaired in patients with AIDS and lymphadenopathy syndrome (LAS). We investigated whether phorbol myristate acetate (PMA) could act in synergy with PHA (as it does in healthy subjects) to enhance in vitro T cell responses of patients at all stages of infection by HIV. In AIDS patients with opportunistic infections (AIDS/OI), PHA + IL-2 + PMA led to a total disappearance of T cell colonies in 10/11 patients, among whom six already displayed very low numbers of colonies induced by PHA + IL-2 (less than 50 colonies/5 x 10(4) cells). In contrast, T cell colony formation induced by PHA + IL-2 + PMA was maintained or increased, compared with that induced by PHA + IL-2, in five out of six AIDS patients with Kaposi's sarcoma (AIDS/KS), 10/14 LAS and six out of seven HIV-seropositive asymptomatic (HIV+/AS) homosexuals. In these three groups of patients, a low percentage of colony cells induced by PHA + IL-2 + PMA expressed CD3 and CD4 molecules, but 50-89% of cells were IL-2R (Tac) positive, as in healthy controls. Studies on T cell activation and IL-2 production were performed on a selected group of 12 HIV-infected patients for whom sufficient numbers of lymphocytes could be obtained. PMA induced CD4 down-modulation in controls and in HIV-infected patients. However, CD3 down-modulation and induction of the Tac chain of IL-2R by PMA were significantly impaired in patients, compared with controls, and these two parameters were correlated. Although PHA alone induced virtually normal levels of Tac antigen on patients' cells, Tac induction by PHA + PMA was significantly decreased in patients versus controls. Cells from five out of 10 patients tested failed to produce detectable amounts of IL-2 after PHA stimulation, whereas IL-2 production increased significantly in all patients tested (n = 9) after PHA + PMA, with a level of IL-2 activity significantly higher than in controls. No correlation was found in this group of patients between the effects of PMA + PHA on T cell colony formation, Tac expression, or IL-2 production, as compared with PHA alone. Taken together, our results indicate that in vitro T cell functional studies with PMA may be useful to evaluate better the defects of T cell activation in HIV-infected patients.

Antigens, CD↗
PubMed1990

Intracytoplasmic detection of the Tac (p55) chain of interleukin-2 receptor in pre-B leukemic cells associated with a constitutive expression of Tac mRNA.

The pre-B Reh-6 leukemic cells do not express membrane interleukin-2 (IL-2)-R alpha (Tac or p55) chain; however, their incubation with PMA induces the expression of both high and low affinity IL-2-R. Northern analysis of nonstimulated Reh-6 as well as leukemic cells from patients with acute B cell precursor lymphoblastic leukemia displayed a constitutive expression of p55 mRNA transcripts, which could be enhanced by PMA. Both actinomycin-D and cycloheximide could abrogate PMA-induced p55 membrane expression, suggesting the need for de novo mRNA and protein synthesis. The increased PMA-induced p55 mRNA accumulation was an early event (4 hr) and could be enhanced, specifically, by rIL-2 because anti-Tac moAb inhibited this rIL-2-mediated effect. Immunofluorescence and cross-linking studies using 125I-rIL-2 failed to reveal membrane-associated p55 protein on both Reh-6 and patients' leukemic cells. Conversely, immunogold staining and electron microscopy studies, revealed p55 immunoreactive molecules in the cytoplasm but not in the nucleus of all Reh-6 cells. Using a sensitive EIA, p55 molecules could be detected in cell lysates but not the culture supernatants of Reh-6 cells, suggesting that p55 was not released into the culture medium. These results indicate that constitutively expressed p55 mRNA on pre-B leukemic cells is translated into a relative immunoreactive protein that cannot be expressed on cell surface for unknown, yet, reasons.

Blotting, Northern↗
PubMed1989

Presence of a p70 IL-2-binding peptide on leukemic cells from various hemopoietic lineages.

Recent studies have shown that IL-2R are composed of at least two polypeptide chains of 55 kDa (Tac or alpha-chain) and 70 to 75 kDa (p70 or beta-chain). The association of both chains forms high affinity IL-2R, whereas each chain alone binds IL-2 with a low (alpha-chain) or intermediate (beta-chain) affinity. So far, the p70 peptide has been found, in the absence of the Tac peptide, on the surface of lymphoid cells of T, B, or NK lineage. In this study, we investigated whether leukemic cells of various hemopoietic lineages expressed the p70 IL-2-binding protein. We found that both fresh leukemic cells obtained from patients, and cells from established leukemic lines of T cells, B cell, and myeloid origin constitutively expressed a p70 IL-2-binding protein on their surface, as detected by affinity cross-linking of radioiodinated IL-2. IL-2 binding and cross-linking to these cells was completely inhibited in the presence of an excess unlabeled rIL-2, but not with an anti-Tac mAb. Binding experiments on pre-B and myeloid cell lines revealed intermediate affinity IL-2R, whereas both high and intermediate affinity IL-2R were detected in T leukemic cells. The intermediate affinity binding of 125I-rIL-2 to the leukemic cell lines MOLT4 and Reh6 was inhibited by the TU27 mAb, which recognized the p75 chain of IL-2R. Moreover, the TU27 mAb could stain the K562, KM3, and MOLT4 (weakly) cell lines by indirect immunofluorescence. A high dose of rIL-2 (400 U/ml) enhanced the proliferation of cells from one out of three patients with acute myeloblastic leukemia, but it did not induce differentiation of the cells in any of three cases. Thus the finding of p70 IL-2-binding molecules on immature lymphoid and nonlymphoid hemopoietic cells should disclose new biologic functions for IL-2.

Cell Differentiation↗
PubMed1987

Specific uptake of alpha-fetoprotein by malignant human lymphoid cells.

We have studied the ability of human B- and T-lymphoblastoid cell lines, as well as of peripheral lymphoid cells from leukemia patients, to take up alpha-fetoprotein (AFP) and other serum proteins. Two technical approaches have been employed, both using fluorescent protein derivatives (FITC-proteins): microscopic examination of labelled cells using epifluorescent illumination and quantitation of endocytosed proteins by fluorescence-activated cell sorting (FACS). Compared to human resting T-lymphocytes, all T- and B-cell lines tested exhibited positive staining for fluoresceinated AFP and transferrin (Tf) and a significant increase, up to 100-fold, of the number of AFP and Tf molecules endocytosed per cell. Labelling was prevented or strongly diminished by a 100-fold excess of unlabelled protein. Preliminary results with peripheral lymphoid cells harvested from leukemia patients showed the presence of AFP- and Tf-positive cells in the blood of all patients examined. Intensity of labelling was related to the type of leukemia cells and/or the degree of cell maturation. Most cell lines exhibited positive staining for alpha 2-macroglobulin (alpha 2M) and also, to a lesser extent, for serum Vitamin D3 binding protein (DBP). In contrast, no labelling was observed with FITC-serum albumin (FITC-Alb) or FITC-ovalbumin (FITC-OVA). Comparative uptake of several FITC-proteins by a single cell population revealed significant quantitative and qualitative differences.

Blood Proteins↗
PubMed1987

Interleukin 2 responsiveness of immature T-cell colony-forming cells (T-CFC) from patients with acute T-cell lymphoblastic leukemias.

T-cell colony-forming cells (T-CFC) from 13 of 17 patients with T-ALL generated colonies in methylcellulose in the absence of added growth factors or mitogenic stimulation. As previously described, these colonies were composed of immature T cells displaying the same karyotypic abnormalities as fresh leukemic cells. Biochemically purified (bIL-2) and recombinant IL-2 (rIL-2) without any mitogen enhanced colony growth from both unfractionated and blast-enriched cell fractions in patients with a relatively low (less than 50 colonies/5 X 10(4) cells) plating efficiency. However, dose-response experiments revealed that the optimal dose of rIL-2 needed to enhance colony growth varied from patient to patient. Anti-IL-2 (DMS1) and anti-IL-2 receptor (anti-Tac) moAbs inhibited both spontaneous and rIL-2-induced colony formation in a dose-dependent manner. Direct staining of fresh leukemic cells with anti-Tac revealed less than 10% positive cells in all but two patients. However, cell incubation in the absence of growth factors or mitogens for 2-48 hr resulted in an increase of Tac+ cells. These observations indicate that a subset of immature T-CFC from T-ALL patients display functional IL-2-receptors. In addition, our findings strongly suggest that the IL-2/IL-2-R system could be involved in the spontaneous proliferation of some immature T-CFC of T-ALL patients.

Acute Disease↗
PubMed1987

Abnormal proliferation of T-colony-forming cells from peripheral blood of patients with T-cell acute lymphoblastic leukaemias and lymphomas in complete remission: potential prognostic value.

Peripheral blood T-colony-forming cells (T-CFC) from most patients with T-cell acute lymphoblastic leukaemias (T-ALL) and T-cell non-Hodgkin's lymphomas (T-NHL), can proliferate in vitro in methylcellulose in the absence of added growth factors or mitogens. We now report that spontaneous T-cell colonies could also be obtained during complete remission of 13 out of 21 patients with T-ALL and T-NHL, but none of eight patients with common (pre-B) ALL (cALL). Colony cells were mainly E+T3+, with a variable expression of other T cell markers. Spontaneous T-CFC did not possess self-renewal capacity in the absence of added growth factors. Moreover, incubation of spontaneous colonies with colchicine yielded mitoses in only two out of seven patients, with one normal and one abnormal karyotype. In five patients tested, recombinant interleukin 2 (IL2) could also induce the proliferation of some T-CFC. Both spontaneous and IL2-induced colonies were inhibited by an anti-IL2 receptor monoclonal antibody, suggesting that interaction of IL2 with its receptor may be involved in the proliferation of some T-CFC from these patients. A study of 14 T-ALL patients tested during their first remission indicated that patients who developed no or few spontaneous colonies during their first remission (less than 20 colonies/10(5) mononuclear cells) seemed to relapse later and to have a significantly longer survival than patients with a high number of spontaneous colonies. These data suggest that the spontaneous proliferation capacity of T-CFC might be of prognostic value in the clinical evaluation of T-ALL.

Adolescent↗
PubMed1987

Characterization of interleukin-2 receptors expressed on acute leukemic B cells.

More than 90% of both unfractionated and blast-enriched T cell-depleted mononuclear cells (MNC) from a patient with a morphologically and phenotypically unclassified acute leukemia expressed interleukin 2 receptors (IL2-R), whereas 50% unfractionated MNC displayed monocyte/myeloid- (My7, My9, and OKM1) and B cell-restricted (B4) antigens. Two-color fluorescence studies showed that 80% of the My9+ cells expressed the B4 antigen and 63% of the B4+ cells were IL2-R+. Cell incubation with phorbol myristate acetate (PMA) increased the expression of B4 antigen and significantly decreased the proportion of My9+ and IL2-R-bearing cells. Southern analysis of DNA from leukemic cells revealed monoclonal rearranged heavy and k light-chain immunoglobulin genes. Immunoprecipitation of leukemic cell membrane proteins with a monoclonal antibody recognizing the IL2-R (anti-Tac) revealed a protein with the same molecular weight (55 kilodaltons) as that of the IL2-R present on PHA-stimulated normal T cells. Fresh leukemic cells did not express high-affinity IL2-R and did not proliferate in liquid culture or in a colony assay in the presence of recombinant IL2 (rIL2). PMA-treated blast cells, however, generated B cell colonies in the presence of rIL2, thus suggesting that PMA could induce functional IL2-R on immature leukemic B cells.

Acute Disease↗
PubMed1986

Media conditioned by human leukemic T-cells induce expression of IL2 receptors and proliferation of normal T lymphocytes.

Peripheral blood T-colony-forming cells (T-CFC) from patients with T-cell acute lymphoblastic leukemias (T-ALL) and T-cell non-Hodgkin lymphomas (T-NHL) can generate colonies in methylcellulose in the absence of added growth factors and/or mitogenic stimulation. In the present study, we show that media conditioned (LCM) by unstimulated mononuclear cells (MNC) from these patients can induce proliferation (proliferating inducing activity; PIA) and promote colony growth (T-cell colony promoting activity; T-CPA) of normal T lymphocytes in the absence of any other mitogenic stimulation. Preincubation of normal E+ lymphocytes with some TCPA+, PIA(-)-LCM for 48 hr leads to IL2-induced cell proliferation in the absence of any other stimulation. Moreover, staining of the cells with anti-Tac monoclonal antibody (Mab) reveal 9%-26% Tac+ cells. Both PIA and IL2 receptor-inducing activities were abrogated by treatment of LCM with proteolytic enzymes or by heating at 47 degrees C for 30 min. Modulation of the T3 molecule by OKT3 MAb on normal E+ cells did not abrogate the capacity of LCM to induce expression of IL2-receptors, suggesting that this activity was not mediated by triggering the Ti-T3 molecular complex. These activities were detected in media conditioned by both unfractionated MNC and blast-enriched cell fractions, and their production required DNA and RNA synthesis by actively dividing cells. Taken together, these findings indicate that human leukemic T cells spontaneously release activities which can activate normal resting T lymphocytes.

Antibodies, Monoclonal↗
PubMed1986

T-cell colony formation in patients with T-cell malignancies: growth factor requirements for in-vitro proliferation of peripheral blood T-cell colony-forming cells.

Peripheral blood T colony-forming cells (T-CFC) from patients with T-cell malignancies are capable of proliferation in methylcellulose, in the absence of added growth factors or mitogenic stimulation. We show here that based on the spontaneous plating efficiencies of their T-CFC, two groups of patients can be established: Group A (10 patients) with a high colony number (more than 100 colonies/10(5) seeded cells), and group B (12 patients) with less than 100 colonies/10(5) cells. The addition of interleukin 2-(IL2) containing PHA-leukocyte conditioned medium enhanced colony growth from group B but not group A patients. Moreover, both biochemically purified and recombinant IL2 induced the colony growth from group B but not group A patients without any other stimulation. In addition, a monoclonal antibody (moAb) against the IL2 receptor (IL2-R; anti-Tac) inhibited the spontaneous colony formation from T-CFC of both groups of patients. These observations strongly suggest that IL2-R are involved in the spontaneous colony growth of T-CFC. To determine whether IL2 is also involved in the spontaneous colony formation, media conditioned (LCM) by unstimulated leukemic cells were tested for IL2 activity. A constitutive release of IL2 was detected in LCM from only 2 out of 10 patients tested, and some of them were capable to inhibit thymidine incorporation by IL2-dependent cells cultured in the presence of highly purified IL2. However, most of these LCM contained a T-cell colony-promoting activity (TCPA) inducing colony formation from both normal resting and PHA-stimulated E+ clonogenic cells without added IL2 or mitogenic stimulation. TCPA-containing LCM induced the expression of functional IL2-R and IL2 release by normal resting lymphocytes. TCPA was constitutively released by blast-enriched cell fractions suggesting that it is released by the leukemic cells.

Antibodies, Monoclonal↗
PubMed1985

Abnormal in vitro proliferation and differentiation of T colony forming cells in AIDS patients and clinically normal male homosexuals.

T cell colonies were generated from the peripheral blood and bone marrow of 11 patients with acquired immune deficiency syndrome (AIDS), 17 normal male and female heterosexuals and seven clinically normal male homosexuals. Mononuclear cells were cultured in methylcellulose both in the absence and presence of interleukin-2 (IL-2) containing conditioned medium. Clinically normal homosexuals showed a low number of T4+ (P less than 0.01) but not T8+ cells. The number of T cell colony forming cells (T-CFC) from both AIDS patients and homosexuals was significantly (P less than 0.01) reduced compared to T-CFC from normal heterosexuals. In seven and four out of 11 AIDS patients, T-CFC from peripheral blood and bone marrow, respectively, were able to generate colonies in the absence of added growth factors and/or mitogenic stimulation. Pooled spontaneous and induced colonies from AIDS patients as well as induced colonies from normal homosexuals were composed of immature cells bearing the T3+, T4+, T6+ T8+ surface phenotype, unlike colonies from normal heterosexuals which displayed mature cells bearing the T3+ T4+ T6- and T3+ T8+ T6- surface phenotype. Moreover, most T-CFC from primary spontaneous and induced colonies had lost their self-renewal capacity either in the absence or the presence of added growth factors. These results suggest that early impairment of T-CFC may play a predominant role in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗