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L Matera

Publications and source records attributed to L Matera.

At least 55 records · Page 3Linked to original sources
PubMed1988

Generation of non-MHC restricted killing in cultures stimulated with B cells from chronic lymphocytic leukaemia patients: phenotypic characterization of the precursor and effector cells.

Freshly isolated B cells from chronic lymphocytic leukaemia patients (B-CLL) have been previously shown to induce a strong proliferative response and high levels of NK-like activity in lymphocytes from healthy donors. The present paper deals with the origin, mitotic state, target spectrum and cell surface phenotype of the NK-like effectors generated after stimulation with B-CLL. Experiments using large granular lymphocytes (LGL) and T cells as responders demonstrated that most of the precursors of the newly generated NK-like effectors express the CD3 antigen. The induction of NK-like activity paralleled cell activation, as judged by blast transformation, thymidine uptake and appearance of cell surface activation markers. The newly generated NK-like effectors displayed a T cell phenotype and a broader target repertoire than native NK cells.

Antigens, Surface↗
PubMed1988

Effect of cortisol on the native and in vitro induced non-MHC restricted cytotoxicity of large granular lymphocytes.

Natural Killer (NK) activity has been shown to be depressed under stressful conditions. Glucocorticoids, which are known to increase during stress, seem to negatively regulate the activity of NK cells. In the present study we have explored the effect of cortisol (hydrocortisone, HC) on NK activity. A significant inhibitory effect could be observed as early as 6 hr after the addition of HC at the concentration of 0.5 microM, corresponding to the upper physiological circulating level. Both the lysis and the binding of the K562 target cells were affected by HC, indicating that the hormone acts on the target recognition phase. The HC-mediated inhibition of the NK activity was fully reversed after 6 hr incubation in a HC-free medium. The observation of comparable levels of NK-inhibition using unseparated PBL or purified LGL, show that HC acts directly on LGL to inhibit their cytotoxic function. The effect of HC on the responsiveness of NK cells to the modifiers beta-interferon (beta-IFN) and recombinant interleukin 2 (rIL2) was also studied. Pre-incubation with HC did not alter the enhancement of the activity induced by beta-IFN, demonstrating that the HC- and beta-IFN-mediated effects occur in separate NK subsets. By contrast the increase of NK cytotoxicity induced by rIL2 was lower in the HC-treated compared to the untreated cell cultures (35.8 +/- 6.2 and 20.7 +/- 4.3% respectively, p less than 0.05) which could indicate that a portion of the cells triggered by rIL2 belong to the HC-sensitive NK subpopulation.

Cell Line, Transformed↗
PubMed1988

Recognition by monoclonal antibody CB02 of a surface molecule shared by B lymphocytes and a discrete large granular lymphocyte subset with cytotoxic activity.

Here we present the characterization of a new antigen called CB02 which is present on B cells and on a subset of CD16+ large granular lymphocytes. The pattern of reactivity of this molecule on normal cells, B cell lines, leukemic cells and tissue sections suggests that the CB02 molecule is expressed by B cells before isotype switch and is lost during terminal differentiation. Furthermore, the CB02+ population encompassed natural killer (NK) cells exerting significant cytotoxic activity: in fact, peripheral blood lymphocytes depleted of the CB02+ subset display a marked reduction in NK activity.

Animals↗
PubMed1987

Aliphatic aldehydes inhibit the proliferative response of human peripheral blood lymphocytes to phytohemagglutinin and alloantigens.

The effect of methyl glyoxal (MG) and various 4-hydroxyalkenals on the response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) or allogeneic cells has been investigated. Pretreatment of PBL with aldehydes significantly reduced the percentage of blast-transformed cells and [3H]thymidine incorporation into DNA in both PHA- and alloantigen-stimulated cultures, hydroxyalkenals being more effective than MG. Further experiments showed that these aldehydes also affected the proliferation of pre-activated lymphocytes. The percentage of blasts as well as [3H]thymidine incorporation into DNA were significantly decreased when the aldehydes were added until 72 h after application of the mitogenic stimulus.

Aldehydes↗
PubMed1987

Generation of non MHC restricted killing in non-cytotoxic T-lymphocytes from leukaemia patients.

Experiments were undertaken to determine whether the depression of natural killer (NK) activity previously observed in the peripheral blood lymphocytes (PBL) of leukaemia patients in remission extended to NK-like precursors in the blood. T-lymphocytes (E+) from leukaemia patients and normal subjects were depleted of IgG Fc-receptor-bearing (gamma FcR) fresh NK cells by passage over immune complex-coated monolayers. gamma FcR - E + PBL were cultured alone or with DAUDI cells. On day 5 of culture, cytotoxicity toward the NK-sensitive cell lines K562 and MOLT-4 was evaluated in the responder lymphocytes of leukaemia patients and controls. Negligible NK-like cytotoxicity was found in both FcR - E + PBL responder populations cultured alone. By contrast, stimulation with DAUDI induced high levels of K562 and MOLT-4 cytotoxicity in leukaemia as well as in normal responder cells. Complement-mediated cytotoxicity experiments using various McAb demonstrated that in both normal and leukaemia cultures NK-like effectors react with the pan-T OKT3 McAb and with the OKT11 McAB directed to the SRBC receptor, but not with Leu 1 1b and OKM1 McAbs, directed against antigens expressed on peripheral blood NK cells. Fractionation of the responder cells on discontinuous Percoll gradients showed that most of this activity was present in the highly dividing blast cell fraction.

Acute Disease↗
PubMed1986

Normal T-lymphocyte function in patients with Hodgkin's disease in long-lasting remission.

In 18 patients with Hodgkin's disease (HD) in long-lasting remission (more than 5 years), the distribution of circulating T-lymphocytes was analyzed using a series of monoclonal antibodies (OKT3, T4, T8, Leu-7, Leu-11 and T10) and correlated with cell function (helper capacity in a pokeweed mitogen system and natural killer (NK) activity). A reduced proportion of OKT4 (helper/inducer)-positive cells associated with a normal absolute number was consistently accompanied by a significant increase (p less than 0.005) in the proportion and absolute number of OKT8 (suppressor/cytotoxic)-positive cells. The OKT4-positive cells, despite their moderate percentage reduction, showed normal helper activity. A more extensive characterization of the lymphoid population in these patients documented a preserved cytotoxic function in a 51Cr release assay and increased proportion of cells expressing NK-associated antigens (Leu-7, Leu-11, OKT10) with a high number of cells coexpressing OKT8 and Leu-7. It is suggested that in patients with Hodgkin's disease in long-lasting remission no laboratory (or clinical) evidence of cellular immunodeficiency can be documented.

Adult↗
PubMed1986

Modulation of in vitro myelopoiesis by LGL: different effects on early and late progenitor cells.

We describe here the modulatory activity of human peripheral blood natural killer (NK) cells on the growth and differentiation of myeloid progenitor cells at different stages of maturation. NK-enriched cell fractions containing 54 to 75% large granular lymphocytes (LGL) and displaying high levels of NK activity significantly inhibited the growth of late (7 day) granulocyte-macrophage colony-forming cells (CFU-GM) from about 50% of normal human bone marrow samples. However, the same fractions strongly enhanced the growth of early (14 day) stem cells from peripheral blood. Enhancing activity on early CFU-GM from blood was greater in highly purified NK cell preparations containing 96% LGL than in NK-depleted T cell preparations from the same donors. Analogous to the results when using the NK-enriched fractions, the NK-purified preparations inhibited late CFU-GM and stimulated the early ones. We conclude from these observations that human LGL have a modulatory effect on myelopoiesis depending on the maturation stage of the progenitor cell.

Bone Marrow Cells↗
PubMed1986

Fc receptor triggering induces expression of surface activation antigens and release of platelet-activating factor in large granular lymphocytes.

Triggering of large granular lymphocyte (LGL) Fc receptor with a specific monoclonal antibody (AB8.28) linked to an insoluble matrix induces cell activation, as witnessed by expression of HLA class II (DR and DQ) molecules and interleukin 2 receptor. Moreover, this event is accompanied by a concomitant release of platelet-activating factor by LGL. We conclude that the Fc receptor molecule identified by mAb AB8.28 represents a trigger for LGL activation.

Antibodies, Monoclonal↗
PubMed1986

Reduced natural killer T-cells in B-cell chronic lymphocytic leukaemia identified by three monoclonal antibodies: Leu-11, A10, AB8.28.

The proportion of E-rosette positive T-lymphocytes capable of reacting with three monoclonal antibodies (MoAbs)--Leu-11, A10, AB8.28--which appear to recognize specifically natural killer (NK) cells, was assessed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). Irrespective of the clinical stage of the disease, the capacity of B-CLL T-lymphocytes to react with all three MoAbs was significantly reduced compared with that of normal circulating T-cells (Leu-11: 2.5% +/- 1.9 SD; A10: 2.3% +/- 1.3; AB8.28: 7% +/- 6.6 v Leu-11: 13.5% +/- 4.5; A10: 8.5% +/- 4.6; AB8.28: 12% +/- 5.5). Furthermore, a marked difference was demonstrated between the reactivity with the Leu-11, A10, AB8.28 MoAbs and the proportion of Leu-7 positive T-cells, which in B-CLL is significantly higher than in normal blood (23% +/- 12.1 v 11.9% +/- 5.9). These findings are in agreement with previous evidence of a discrepancy in B-CLL between the phenotypic expression, assessed by Leu-7 positivity, and the true functional activity of NK T-cells, and suggest that the Leu-11, A10 and AB8.28 MoAbs correlate well with the depressed NK function found in this disease.

Antibodies, Monoclonal↗
PubMed1986

Phenotypic and functional characterization of the circulating NK compartment in hairy cell leukaemia.

A phenotypic and functional analysis of the circulating natural killer (NK) cell population was carried out in a series of patients with hairy cell leukaemia (HCL). The overall mean NK activity of both the mononuclear and T cell fractions was reduced compared to that of normal controls (466 lytic units (lu) v 573 lu and 226 lu v 381 lu, respectively), though this difference did not reach statistical significance (P less than 0.05). Individual analysis of the data showed that in five out of 15 and in seven out of 16 cases the K562 killing by the mononuclear and T cells respectively was below the lowest s.d. limit for normal subjects. This reduced NK function was associated with a decreased ability of the effector cells to bind the target. The NK response to exogenous human leucocyte interferon was also generally depressed in cases with a low basal NK activity. The functional studies were complemented with the evaluation of the membrane expression of NK associated antigens. The percentage of circulating T cells recognized by the monoclonal antibody (MoAb) Leu-7 was significantly higher (P less than 0.001) in HCL than in normal blood (25.2% +/- 10.2 v 11.9 +/- 5.9 s.d.). However, the reactivity with two other NK-related MoAb, Leu-11 and AB8.28, was significantly lower (7.1% +/- 6.9 and 9.8% +/- 8.5; P less than 0.002) than with Leu-7 and moderately reduced compared with that of normal circulating T cells (11.7% + 6.1 & 12% + 5.5). These findings suggest that in a proportion of patients with HCL there is an impairment of the NK compartment, which may contribute towards the occurrence of the infective complications which are the primary cause of death in this disease.

Antibodies, Monoclonal↗
PubMed1985

Murine monoclonal antibodies as probes for the phenotypical, functional, and molecular analysis of a discrete peripheral blood lymphocyte population exerting natural killer activity in vitro.

Two monoclonal antibodies (AB8.28 and A10) reacting with large granular lymphocytes were extensively studied and characterized. The two peripheral blood lymphocyte subsets positive for the expression of AB8.28 and A10 determinants were isolated by cell sorting and the phenotype analyzed using a panel of anti-lymphocyte reagents. Both subsets displayed the characteristics of "null cells." Moreover, these subsets encompassed a significant amount of the natural killer activity, since preparations of peripheral blood lymphocytes deprived of AB8.28+ and A10+ cells showed a remarkable reduction of such activity. The analysis of the distribution of the AB8.28 and A10 epitopes has been carried out using a variety of cells, i.e., normal tissues, tumor cells, established cell lines, and preparations obtained from patients with different leukemic disorders. The structure bearing the epitopes recognized by the two monoclonal antibodies was characterized immunologically (immunoprecipitation, SDS-PAGE analysis, immunomodulation, and competition with other antibodies) and by various functional assays. On the basis of inhibition tests, the AB8.28 molecule seems to be related functionally and/or structurally with the IgG Fc receptor. By contrast, the A10 structure does not share this activity and so far has eluded any precise biological characterization.

Antibodies, Monoclonal↗
PubMed1985

A novel leukemia T-cell line (PF-382) with phenotypic and functional features of suppressor lymphocytes.

A human leukemia T-cell line (PF-382) spontaneously derived from the pleural effusion of a child with T-cell acute lymphoblastic leukemia is described. The cell line, which has been maintained in culture for over 10 months, has a modal number of 46 chromosomes and is characterized by a chromosomal abnormality, present in most of the cells, consisting of a translocation between chromosome X and chromosome 15 (46X,Xq-,15p+). The cells are not recognized by the OKT3 and OKT11 monoclonal antibodies (MoAb), nor do they form rosettes with sheep erythrocytes. By contrast, they react with the OKT6, Leu-1, and Leu-9 MoAb, which detect early T-lymphocytes, and express the more mature OKT8 antigen. The presence of the OKT8 marker is associated with suppressor activity on the pokeweed mitogen-induced proliferation and differentiation of normal B-cells, both by the PF-382 cells and by their supernatant. However, no cytotoxic activity against natural killer (NK)-sensitive target cells (K562) was found, indicating that the proliferating cells do not correspond to the subset of NK cells expressing the OKT8 antigen. Furthermore, the cells are incapable of both spontaneous and mitogen-induced interleukin-2 and interferon production. The ability of the PF-382 cell line to release a soluble factor(s) capable of modulating the differentiation of the B-cell compartment suggests that this new cell line represents a valuable model for the investigation of the interrelationships between T-cell subsets and other hematopoietic cell lineages.

Antigens, Viral↗
PubMed1985

Generation of natural killer-like activity in mixed lymphocyte-tumor cell cultures. II. Correlation between expression of HLA-DR antigens on the activated T cells and their cytotoxic capability.

In this study, we investigated the role of DR antigens in human mixed lymphocyte reactions (MLR) at the responder cell level. Upon stimulation by allogeneic lymphocytes or leukemic cell lines, a large proportion of T cells underwent blastogenesis and began expressing DR antigens. Analysis by a fluorescence-activated cell sorter revealed that both subpopulations of large activated T cell blasts and of small T lymphocytes became DR+ by synthesis and/or uptake. Depletion of DR+ responder cells from 6-day-old MLRs by treatment with anti-DR monoclonal antibodies (mAbs) plus complement (C) reduced but did not completely abrogate the natural killer (NK)-like activity of the responder lymphocytes, suggesting that the MLR-induced cytotoxic cells include both DR+ and Dr- populations. The expression of NK-like activity by the responder cells was also greatly reduced upon addition of anti-DR mAbs (without C) at the start of the mixed cultures. This effect was observed regardless of the presence of DR antigens on the stimulator cells, indicating that the anti-DR mAbs can interact with the antigens present on both the stimulator and responder populations. These data show that during an MLR, the continued presence of DR antigens on the responding population is essential for the expression and maintenance of the proliferative and cytotoxic capabilities of these cells.

Antibodies, Monoclonal↗
PubMed1985

Generation of natural killer-like activity in mixed lymphocyte-tumor cell cultures. I. Role of HLA-DR antigens as stimulatory molecules.

A number of human lymphoid and non-lymphoid leukemic cell lines differing for expression of HLA-DR antigens were analyzed for the ability to induce natural killer(NK)-like activity and proliferation in lymphocytes from healthy donors. The ability to elicit the generation of NK-like activity in the responder lymphocytes varied greatly depending upon the type of antimitotic treatment (gamma-irradiation versus mitomycin C) received by the tumor cells prior to the start of the mixed cultures. By contrast, the induction of T-cell proliferation was positively correlated with the presence of DR molecules on the tumor cell lines. Nevertheless, DR- leukemic cells pretreated with the appropriate antimitotic agent did induce a proliferative response in the mixed cultures. T lymphocytes cultured without stimulator cells in spent medium containing high levels of cell-free DR antigens failed to undergo blastogenesis and proliferation, indicating that DR antigens can function as stimulatory molecules only when they are cell-associated.

Cell Line↗
PubMed1984

Discrepancy between phenotypic and functional features of natural killer T-lymphocytes in B-cell chronic lymphocytic leukaemia.

The phenotypic expression and functional capacity of natural killer (NK) T-lymphocytes (E+, OKT3+) were analysed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). The mean value of NK activity of B-CLL T-lymphocytes, tested against the K562 cell line, was significantly depressed (P less than 0.01) in the 20 cases studied, compared with that of normal T-cells. Incubation with human leucocyte interferon produced an increase (P less than 0.05) in NK activity, although the mean value was still significantly lower (P less than 0.05) than that obtained with normal T-cells. Furthermore, the formation of effector-target conjugates was significantly lower (P less than 0.01) among B-CLL T-cells compared with normal T-lymphocytes. Despite the reduced NK functions observed in the majority of B-CLL patients, the capacity of T-cells to react with the monoclonal antibody (MoAb) Leu-7 (HNK-1 clone), assessed in 60 patients, was significantly higher (P less than 0.001) in B-CLL than in normal blood (mean 24% +/- 10.6 SD v 9% +/- 4.2), irrespective of the clinical stage of the disease. These findings suggest that the reduced cytotoxic ability of B-CLL T-lymphocytes may be due either to an expanded population of immature T-cells which already express a cytotoxic-like phenotype (E+, OKT3+, HNK-1+) but which lack adequate cytotoxic functions, or, alternatively, to an intrinsic defect of the natural effectors present within the T-cell population of B-CLL. The T-cell functional abnormalities documented in this study, together with other defective functions previously described, may be implicated in some of the complications frequently associated with B-CLL, particularly the high incidence of secondary neoplasms. There is growing evidence that natural cytotoxicity may play a major role in the immune surveillance system, both against tumour cells and virus-infected cells (Herberman & Ortaldo, 1981). Natural killer (NK) cells are a morphologically homogeneous population of large granular lymphocytes with azurophilic granules in the cytoplasm (Timonen et al, 1981), which are non-adherent and express receptors for the Fc portion of IgG. About 50% of these cells form rosettes with sheep red blood cells (E-rosettes) (West et al, 1977). A monoclonal antibody (MoAb) which appears to react with practically all human NK cells (HNK-1 clone, Leu-7; Becton Dickinson) has been recently produced (Abo & Balch, 1981).(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1984

In vitro generation of NK-like activity in human PBL co-cultured with fresh T leukaemia cells.

Generation of cytotoxic activity attributable to natural killer (NK)-like effector cells, against the NK-sensitive erythroleukaemia cell line K562 was estimated in peripheral blood lymphocytes (PBL) from normal donors, following stimulation with fresh leukaemic cells (FLC) of T-origin. One of 9 FLC induced anti-K562 cytotoxicity which was considerably higher than that of unstimulated control PBL. Cells derived from this patient possessed acid phosphatase (AP) and TdT activity. The reacted with the monoclonal antibodies RFA1 (directed against early and mature T cells) and A10 (specific for lymphohaemopoietic precursors). However, the cells did not form E rosettes, nor did they react with the monoclonal antibodies OKT3, OKT4, OKT8 and OKT11 to human T cell surface antigens. OKT6, which recognizes 70% of thymic lymphocytes was also negative. The high stimulatory activity of these cells may be related to the expression of surface determinants characteristic of early stages of the T-cell pathway, detected only by the monoclonal antibody RFA1.

Antibodies, Monoclonal↗