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Biomedical subjects

C Russo

Publications and source records attributed to C Russo.

At least 145 records · Page 8Linked to original sources

Complement-dependent killing of human hematopoietic progenitor cells with noncomplement-fixing monoclonal antibodies in an antiglobulin assay.

A complement (C)-dependent antiglobulin assay was utilized to determine the reactivity of non-C-fixing monoclonal antibodies (MoAb) with human granulocyte-macrophage progenitor cells (CFU-GM). The variables of the assay were analyzed with non-C-fixing MoAb against Ia antigens, including CR11-462, which recognizes the same (or spatially close) determinant identified by the C-fixing anti-Ia MoAb Q5/13. The sensitivity of the antiglobulin assay was influenced by dilutions of anti-mouse Ig xenoantiserum and of rabbit C. Five non-C-fixing MoAb to Ia antigens, seven non-C-fixing MoAb to HLA-A,B antigens, and one non-C-fixing MoAb to beta 2-microglobulin induced marked inhibition of human CFU-GM in the antiglobulin assay. The activity of non-C-fixing MoAb in the antiglobulin assay was comparable to that of C-fixing anti-Ia and anti-HLA-A,B MoAb in the standard cytotoxicity assay. In addition, the cytotoxic effect of dilute C-fixing anti-Ia MoAb was enhanced when the antiglobulin technique was employed. The results of this study indicate that the antiglobulin assay is a rapid and simple technique for the characterization of antigens on human hematopoietic progenitors. Our data also indicate that Ia antigens are expressed on most CFU-GM and that the conflicting results in the literature (that is, those suggesting that Ia antigens are expressed on a smaller proportion of CFU-GM) may reflect differences in the cytolytic activity of the MoAb and rabbit C used.

Adult↗

Lactate dehydrogenase isoenzyme activity in malignant haematological diseases.

The isoenzymes 1 and 2 (LDH1 and LDH2) of lactic dehydrogenase (LDH) were studied in the serum of 32 patients with malignant haematological diseases. In non-Hodgkin lymphoma (NHL) a diminution in LDH1 and an increase in LDH2 was a sign of evolution towards a more aggressive phase of the disease, or the absence of clinical remission, even when no significant variation of total LDH can be observed in the serum. In acute lymphoblastic leukaemia (ALL), the isoenzymatic variations are not an early indication of relapse. No significant variations in serum LDH or of these isoenzymes was observed in chronic lymphocytic leukaemia (CLL) or Hodgkin's disease (HD). Only in NHL did the variations of LDH1 and LDH2 appear to be a biochemical marker of the tumour process and of cellular differentiation.

Hematologic Diseases↗

The monoclonal antibody CR11-351 discriminates HLA-A2 variants identified by T cells.

Serologic and immunochemical assays have shown that the monoclonal antibody (MoAb) CR11-351 recognizes a determinant expressed by HLA-A2 and A28 alloantigens. The MoAb CR11-351 blocks the cytotoxicity of some, but not all, anti-HLA-A2 and anti-HLA-A28 alloantisera tested. These findings suggest that each allospecificity consists of several determinants, only some of which are spatially close to the determinant defined by the MoAb CR11-351. The binding of the MoAb CR11-351 to HLA-A2 lymphoid cells is not effected by their precoating with the HLA-A, B-specific MoAb CR10-214, Q6/64, and 6/31 but is enhanced by at least 20% by the MoAb CR10-131, CR10-402 and by the beta 2-m-specific MoAb NAMB-1. The MoAb CR11-351 did not react with one of four HLA-A2 variants which are indistinguishable with conventional anti-HLA-A2 sera, but are not recognized by "normal" HLA-A2-restricted cytotoxic T cells and possess structurally distinct HLA-A2 heavy chains. Therefore the MoAb CR11-351 provides the first evidence of a serologically detectable difference between the four HLA-A2 variants and "normal" HLA-A2 antigens.

Antibodies, Monoclonal↗

Inhibitory effect of a low dose of prednisone on PHA-induced Ia antigen expression by human T cells and on proliferation of T cells stimulated with autologous PHA-T cells.

Administration of a small dose of prednisone markedly reduced (1) the PHA-induced expression of Ia antigens by T cells, (2) the stimulatory activity of Ia antigen-bearing T cells in autologous and allogeneic mixed lymphocyte reactions (MLRs), and (3) the proliferative response of T cells stimulated with autologous PHA-activated T cells or autologous or allogeneic non-T cells. The inhibitory effects of prednisone are reversible and are not detectable on T cells isolated from blood drawn 24 hr following prednisone administration. The kinetics of the prednisone-mediated inhibition of MLRs with autologous PHA-T cells is different from that of MLRs with autologous non-T cells. These data in conjunction with the information available in the literature suggest that the mechanisms underlying these two types of autologous MLRs are different.

Adult↗

Human T lymphocytes in aging and malignancy: abnormalities in PHA-induced Ia antigen expression and in functional activity in autologous and allogeneic MLR.

T lymphocytes from patients with solid tumors and from aged donors are abnormal in their expression of Ia antigens following in vitro stimulation with phytohemagglutinin (PHA). Ia antigens were not detected on PHA-activated T lymphocytes from 15 of 27 patients with solid tumors. The abnormality in T lymphocytes from 25 donors older than 60 years was evidenced by a reduction in the percentage of T cells acquiring Ia antigens following stimulation with suboptimal amounts of PHA and by a delayed appearance of those antigens. In both groups of donors the defect in Ia antigen expression by PHA-activated T cells did not correlate with the reduced [3H]thymidine uptake. PHA-activated T cells from aged donors and from patients with solid tumors were poorly stimulatory in autologous and allogenic mixed lymphocyte reactions. Furthermore, T lymphocytes from these two groups of donors displayed a reduced proliferative response to autologous non-T cells, but a normal proliferative response to allogeneic PHA-activated T cells and to non-T cells from control subjects.

Adult↗

Role of distinct domains of Ia antigens in autologous and allogeneic mixed lymphocyte reactions.

Murine monoclonal antibodies (MoAb) to distinct determinants of human Ia antigens and low doses of prednisone induce different effects on the autologous mixed lymphocyte reaction (MLR), stimulated by PHA-T cells or by non-T cells, and on allogeneic MLRs. These results suggest that distinct domains of Ia antigens and/or mechanisms are involved in these types of MLRs.

Antibodies, Monoclonal↗

Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions.

The antigenic heterogeneity of primary and metastatic lesions surgically removed from nine patients with nodular melanoma was investigated by using monoclonal antibodies to HLA-A, B antigens, to beta 2-microglobulin, to Ia antigens, and to melanoma-associated antigens (MAA). The latter include three types of membrane-bound MAA and a cytoplasmic MAA. In spite of an homogeneous morphologic appearance, multiple lesions removed from the same patient differed significantly in their reactivity with the panel of monoclonal antibodies in indirect immunofluorescence test. The extent of antigenic heterogeneity did not correlate with melanin synthesis, site of origin of the primary tumor, site of metastatic foci, or treatment, but was less marked in patients carrying the primary tumor. The antigenic heterogeneity of multiple lesions removed from one patient and the independent expression of the various types of MAA investigated suggest that combinations of monoclonal antibodies to MAA may be more effective than single antibodies for radioimaging and immunotherapy.

Antibodies, Monoclonal↗

An antiglobulin microcytotoxicity assay to analyze non-complement fixing monoclonal antibodies to human histocompatibility antigens.

An antiglobulin microcytotoxicity assay has been used to analyze non-complement fixing monoclonal antibodies to human histocompatibility antigens. The assay utilizes methodology similar to that of the widely used microcytotoxicity assay for HLA typing, requires low numbers of target cells and is suitable to test large numbers of samples. The sensitivity of the assay is influenced by the anti-mouse Ig antiserum used, by the sequence of addition of the various reagents and by the incubation time. The assay is suitable to screen supernatants of clones derived from hybridization experiments and to characterize the serological specificity of anti-HLA monoclonal antibodies.

Animals↗

In vitro-isolated human cytotoxic T-lymphocyte clones detect variations in serologically defined HLA antigens.

T cells of two donors, JR (HLA-A23,29;B7,7;C-;DRw5) and HG (HLA-A2,23;B40,w44;Cw4), were stimulated with cells from an HLA homozygous lymphoblastoid cell line JY (HLA-A2,2;B7,7,C-,DRw4,6) and cloned by limiting dilution after the third stimulation. Two cytotoxic T-cell (CTL) clones, JR-2-16 (from donor JR) and HG-31 (from donor HG), were used for detailed studies. The results of a panel study using lymphocytes from HLA-typed individuals and a study with two HLA recombinant families indicate that the antigens recognized by the CTL clones JR-2-16 and HG-31 were highly associated with HLA-A2 and HLA-B7, respectively. Blocking studies with a monoclonal antibody recognizing a framework determinant on HLA-A, -B and -C antigens and a monoclonal antibody reacting with HLA-A2 support the notion that JR-2-16 and HG-31 interact with the HLA-A2 and the HLA-B7 antigens per se. However, these clones did not recognize the HLA-A2 and HLA-B7 of all donors typed for these antigens, suggesting that the HLA-A2 and HLA-B7 antigens of these particular donors are variants of the serologically defined HLA antigens. These results indicate that in vitro-derived human CTL clones detect variations in the serologically defined allospecificities and can be used as reagents to elucidate the polymorphism of HLA antigens further.

Antibodies, Monoclonal↗

Immunochemical analysis of anti-HLA-A2, HLA-A3, and HLA-B27 xenoantisera elicited with hybrids between human and murine cells.

Rabbits were immunized with hybrids constructed with human and murine cells. Serological and immunochemical studies showed that xenoantiserum 1595 is operationally specific for HLA-A2, xenoantisera 0806 and 0746 for HLA-A3 and xenoantiserum 0745 for HLA-B27. The Fab2 blocking assay suggests a spatial relationship between allotypic determinants recognized by the xenoantisera and those reacting with the HLA-A, B-specific monoclonal antibodies (MoAb) Q1/28, 6/31, Q6/64, and CR-1 and the anti-beta 2-microglobulin (beta 2-mu) MoAb NAMB-1.

Animals↗

Stimulation of human T lymphocytes by PHA-activated autologous T lymphocytes: analysis of the role of Ia-like antigens with monoclonal antibodies.

Human T lymphocytes activated with PHA express Ia-like antigens and acquire the ability to stimulate autologous T lymphocytes in mixed lymphocyte reaction. This reaction is immunological in nature since it has specificity and memory. Ia-like antigens play a role in the stimulation of T lymphocytes by autologous PHA-T lymphocytes since monoclonal antibodies to Ia-like antigens can significantly, although not completely, inhibit the stimulation.

Antibodies↗