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Biomedical subjects

M Benczur

Publications and source records attributed to M Benczur.

At least 37 records · Page 2Linked to original sources
PubMed1985

Mapping the functional topography of Fc gamma with monoclonal antibodies: localization of epitopes interacting with the binding sites of Fc receptor on human K cells.

A panel of monoclonal antibodies (mAb) specific for the C gamma 2, C gamma 3 or inter C gamma 2/C gamma 3 domain epitopes was tested for inhibition of antibody-dependent cellular cytotoxicity (ADCC) specific for anti-D IgG-coated erythrocytes. Significant inhibition of ADCC was demonstrable for some antibodies having specificity for C gamma 2 or C gamma 3 domain epitopes, while others gave no inhibition. Fab fragments of a representative C gamma 2-specific antibody (A55) and C gamma 3-specific antibody (x3a8) retained their inhibitory capacity in lymphocyte-mediated ADCC, but only A55 Fab inhibited monocyte-mediated lysis. Furthermore, the Fab portion of A55 completely abolished the complement-dependent enhancement of ADCC mediated by concanavalin A-stimulated cells, while x3a8 Fab had no effect in this system. On the other hand, x3a8 Fab inhibited the binding of anti-D IgG-sensitized erythrocytes to lymphocytes while A55 Fab did not influence this latter interaction. The results suggest that C gamma 2 domain-FcR interaction is essential for the triggering of lytic process both in lymphocyte and in monocyte-mediated ADCC, while C gamma 3 domain has no role in the latter but is responsible for the appropriate contact between effector lymphocytes and target cells. A site in the region of Lys274 appears to be critical for triggering of both lymphocyte and monocyte-mediated ADCC.

Antibodies, Monoclonal↗
PubMed1984

Ligand inhibition studies on the role of Fc receptors in antibody-dependent cell-mediated cytotoxicity.

Subjection of human peripheral blood lymphocytes to a temp shift from 4 to 37 degrees C resulted in a shedding of Fc receptors (termed FcRI) from 40-50% of FcR-positive cells followed by their re-expression within 4 hr; a phenomenon which had no effect on the cells' antibody-dependent killing capacity. Removal of lymphocytes having an immobile form of the Fc receptor resistant to the effects of the temp shift (termed FcRII), or removal of lymphocytes bearing both FcRI and FcRII, resulted in a similar amount of reduction in ADCC activity. This was attributed, therefore, to the loss of FcRII-positive cells. The influence of isolated (shedded) FcRI and Clq on ADCC activity was investigated. Soluble FcRI was shown to inhibit ADCC mediated through the immobile Fc receptors (FcRII), despite its lack of an ability to block EA rosette formation through these receptors. Clq also had a dose-dependent inhibitory effect on ADCC. These observations are consistent with earlier findings that FcRII possesses two active binding sites; and suggest that a prerequisite for killing in ADCC is the interaction of these with the C gamma 2 and C gamma 3 domains. The ability of synthetic peptides representative of human gamma 1-chain sequences to inhibit ADCC was determined, in an attempt to locate those sites within the IgG antibody Fc region involved in interaction with two FcR binding sites. Preliminary evidence was obtained to suggest that one of these is situated within the C gamma 2 domain, in the region of residues 274 (Lys)-294 (Glu).

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

C3 cleaved by membrane proteases binds to C3b acceptors expressed on concanavalin A-stimulated human lymphocytes and enhances antibody-dependent cellular cytotoxicity.

On activation of cells membrane-associated proteases--including serine esterases known to cleave the third component of complement (C3)--become expressed. In this paper it is shown that as a consequence of this enzyme activity isolated native human C3 added to concanavalin A (Con A)-activated human lymphocytes is cleaved on the surface of the blast cells. This enables the immediate fixation of nascent C3b (C3bx) through its short-lived metastable binding site to C3b acceptors (C3bA's) newly expressed on Con A-stimulated cells. Acceptor-bound C3b is detected by the immune adherence rosette formation of the C3-treated Con A blasts with the C3b receptor (C3bR)-bearing O, Rh+ erythrocytes (32 +/- 4%). The cleavage of C3 and the covalent fixation of C3b are shown to be inhibited by phenylmethylsulphonyl fluoride and methylamine, respectively. As a functional consequence of the covalent fixation of C3b to the mitogen-activated lymphocytes it is demonstrated that the antibody-dependent cellular cytotoxicity (ADCC) of these cells against O, Rh+ erythrocytes sensitized with anti-D IgG is significantly enhanced. The C3 specificity of the process and the role of C3bR's of the target cells are proved. It is postulated that effector cell-bound C3b amplifies ADCC by improving effector cell-target cell contact.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Recognition of autologous and allogeneic lymphocytes and tumor cells by human natural killer cells.

The shedding of the mobile Fc receptor (FcR1) and the depletion of the immobile Fc receptor (FcR11) bearing human lymphocytes revealed that human natural killer cells belong to the FcR11-bearing population. Anti-beta-2-microglobulin treatment of the effector cells decreased natural cytotoxicity against some target cells and the detectability of HLA antigens, indicating that histocompatibility antigens or related structures may be involved in natural cytotoxicity. Using a panel of 29 autologous and allogenic PHA-stimulated target cells and peripheral lymphocytes from the same donors as the effector cells, distinct cytotoxic responses against allogeneic and autologous target cells were observed. A computer analysis of selective natural cytotoxicity distinguished seven different groups of target cells that may represent common structures for NK recognition.

Cell Line↗
PubMed1982

Association between HLA B7, DR2 and dysfunction of natural- and antibody-mediated cytotoxicity without connection with the deficient interferon production in multiple sclerosis.

In this study, 133 patients with MS were investigated for HLA-A,B,C,DR antigens, natural killer (NK) cell activity, and antibody-mediated cytotoxicity (ADCC). A higher frequency of HLA B7 and DR2 was found in this group of patients than in the healthy control group, as can be observed in other caucasoid populations as well. In Gypsies living in the same geographic area, almost a complete absence of the disease was observed, corresponding to a lack of B7; however, HLA DR2 was present in 56% of this population. NK activity and ADCC measured against the K-562 tumor cell line was found to be significantly lower in MS patients, most pronounced in the group of male patients. Interferon augmentation of NK activity showed similar impairment in the patient group, and their lymphocytes produced a significantly lower amount of interferon. A correlation was demonstrated between both killer cell function and HLA B7, DR2 in MS patients, however, it was significant only in the case of ADCC and DR2. No other correlations were found in relation to interferon augmentation, interferon production, and HLA antigens. The above finding underscores a possible HLA-linked pathogenetic role of NK and K cell dysfunction in MS. This is consistent with other, similar observations that a possible defect in virus immunity may exist in MS patients.

Adult↗
PubMed1982

Natural killer lymphocyte function in cervical cancer patients.

Authors investigated the natural killer and antibody dependent cellular cytotoxicity functions of lymphocytes in cervical cancer patients. According to the results the natural killer function showed remarkable changes related to the extent and the course of the disease. On the contrary, radiation therapy did not influence this function. The antibody dependent cellular cytotoxicity function of the same lymphocytes did not show any alteration under circumstances mentioned above.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Increased killer cell activity in aged humans.

Natural cell-mediated cytotoxicity (NCMC) against a cell line (K-562) and antibody-dependent cellular cytotoxicity (ADCC) against the same target and against chicken red blood cells were investigated in two age groups (20--45 and 70--98 years old). Proliferative response to PHA and to allogenic cells as well as some subpopulation determinations were also carried out only lymphocytes of the same subjects. In contrast to the significantly decreased proliferative responses, NCMC showed a moderate, and the two ADCC values a highly significant increase in the group of aged subjects. These increased values showed some similarities with the quantitative changes within the T-lymphocyte subpopulations. The incidence of serum samples of NCMC inhibitory activity was only moderately increased in the group of aged subjects as compared to that of the young individuals. On the basis of these results, we concluded that the immune system of healthy aged subjects seems altered or inbalanced rather than depressed to that of the young individuals.

Adult↗
PubMed1981

[Association between natural cell mediated cytotoxicity (NCMC) and serum factors in acute leukemia and other malignant diseases].

Natural cell-mediated cytotoxicity (NCMC) of human peripheral lymphocytes against allogeneic tumor line (K-562) was substantially increased by the AB serum. Dialysis, a well as Sephadex G-200 gel filtration of AB serum revealed that the immunoglobulin containing fraction was the responsible factor for the increase. Results suggest the involvement of antibodies in NCMC. Autologous and allogeneic serum of patients with gynecological carcinoma inhibited (10-64%) and/or stimulated (10-250%) the NCMC activity in the patients. Residual NCMC activity exceeding 20% has been present after the trypsin digestion in serum free medium of effector lymphocytes. A similar 20% residual activity has been observed after the addition of anti-immunglobulin and antigen-antibody complexes, respectively. Our findings suggested the role of antibodies and serum factors in natural killer activity. Nonetheless other mechanisms resistant to trypsin treatment and of a certain specificity to tumor cells may not be excluded.

Animals↗
PubMed1980

Dysfunction of natural killer cells in multiple sclerosis: a possible pathogenetic factor.

Natural killer (NK) cell activity, antibody-dependent cytotoxicity (ADCC) and the effect of interferon on NK activity was investigated in multiple sclerosis (MS) patients. NK activity measured against K-562 tumour cell line was found to be significantly low in MS patients, and this was most pronounced in the group of male patients with definitive disease. The response of NK cells to interferon proved to be impaired and almost no activation could be demonstrated in response to polyinosinic-polycytidylic acid (poly I:C). Preliminary data obtained by the determination of interferon production in several definitive MS cases reflect a defect in the interferon producing capacity of lymphocytes. The possible involvement of impaired NK cell function in the aetiopathogenesis of MS is discussed.

Adult↗
PubMed1979

Characteristics of different rhesus alloantibodies in lymphocyte dependent (K cell) cytotoxicity to human erythrocytes.

The property of rhesus alloantibodies to elicit antibody-dependent, cell-mediated cytotoxicity (ADCC) against target erythrocytes carrying various Rh genotypes was studied. The killer activity of normal peripheral lymphocytes on human erythrocyte target cells carrying the appropriate antigens elicited by alloantisera was measured by 51Cr release at 18 h. There was no correlation between ADCC and antibodies directed to the antigens present on the surface of different genotypes of Rh-positive red blood cells. The agglutinin titre of different Rh antibodies showed no correlation with the level of ADCC although the degree of cellular cytotoxicity was different with different anti-D sera. Anti-C + D+ E antibody caused higher ADCC than anti-C + D and the lowest cytotoxicity was observed with anti-D and anti-D+ E. This raised the possibility that ADCC was elicited by antibodies directed to other specificities. K cell lysis of human red cells by human peripheral blood lymphocytes in vitro suggests that a similar mechanism may operate in vitro in the destruction of erythrocytes coated by allo or autoantibodies.

Animals↗
PubMed1979

Correlation between effector lymphocytes in natural and antibody-mediated cytotoxicity.

Human sera enhanced spontaneous cell-mediated cytotoxicity (SCMC), while anti-IgG (Fab') 2 treatment decreased this cytotoxic activity of human lymphocytes for an in vitro growing cell line (K--562). Trypsin treatment of the effector cells considerably decreased the cytotoxic potential. However, a significant cytotoxic activity could always be found in serum-free medium. While these findings suggest the involvement of antibodies in the SCMC, they also reflect the existence of serum-indpendent (sui generis) SCMC activity of lymphocytes. Removal of SCMC of Fc receptor bearing effector cells was performed by target cell adherence (rosetting). Separation of the target cell-bound lymphocytes was done by centrifugation on special Ficoll gradient. The depletion of SCMC effector cells resulted in a 62% reduction of SCMC and in a 39% reduction of ADCC. On the other hand, removal of Fc bearing effector cells showed a similar reduction in both ADCC (66%) and SCMC (78%). Our results suggest that SCMC represents a complex activity, arising partly from the interactions of certain serum-derived or lymphocytes surface-bound antibodies and partly from a spontaneous cytotoxic function of the effector cells. It is possible that the effector cells involved in both SCMC and ADCC derive from the same lymphocyte population and the differences are due mainly to the lower number of SCMC effector cells.

Animals↗
PubMed1979

The natural killer activity (cytotoxicity) of lymphocytes.

The authors' own investigations into the spontaneous lymphocyte-mediated cytotoxicity (SLMC) have been reviewed and discussed in th light of literary data. It is suggested that SLMC is a resultant of complex effects contributed by antibodies present in the human serum and those attached to the surface of lymphocytes as well as by spontaneous (sui generis) functions of effector cells. The lymphocytes eliciting SLMC belong to the "O" subpopulation, bear Fc receptors and are presumably, identical with "K" lymphocytes. In animal experiments, the authors have shown that the SLMC reaction directed againt a virus-induced tumour is under polygenetic control primarily governed by gene(s0 linked to the histocompatibility region. In man, similarly as in the mouse, SLMC was found to be a genetically-controlled lymphocyte function in which gene(s) linked to the HLA-A2 B12 or the HLA-A3 B7 haplotype may play a determining role. The authors' clinical observations indicate that LSMC represents an important part of the defense mechanism against malignancies and autoimmune diseases. Estimation and follow-up of SLMC may be useful in monitoring the clinical course.

Animals↗
PubMed1977

Antibody dependent and spontaneous lymphocyte mediated cytotoxicity in normal subjects, patients with SLE, and malignancies.

Antibody dependent and spontaneous lymphocyte mediated cytotoxicity was studied in healthy subjects and patients with systemic lupus erythematosus and metastatic tumours. The purified peripheral blood lymphocytes of healthy subjects exerted a similar cytotoxic activity on allogeneic K-562 and xenogeneic chicken erythrocyte targets in the antibody dependent and spontaneous lymphocyte mediated cytotoxicity tests. There was a stronger correlation between the cytotoxicity measured in the two allogeneic assays than between allogeneic and xenogeneic tests. Allogeneic systems using K-562 targets were more sensitive to changes in cytotoxic activity in systemic lupus erythematosus and metastatic tumours than was the xenogeneic chicken erythrocyte assay.

Antibody-Dependent Cell Cytotoxicity↗