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Biomedical subjects

M Takasugi

Publications and source records attributed to M Takasugi.

At least 109 records · Page 6Linked to original sources
PubMed1978

Specificity and effector-target interaction.

When effector cells were tested on a number of target cells, the most obvious effect observed was a nonselective cytotoxicity that is now known as natural cell-mediated cytotoxicity. The apparent nonselectivity was a result of specific cytotoxic activity against many different antigens on target cells. This specificity was demonstrated in the cross-competition assay in which target cells sharing common antigens selectively inhibited natural cytotoxicity.

Cross Reactions↗
PubMed1977

Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum.

When effector cells from most individuals are tested directly against a number of target cells for cell-mediated cytotoxicity, most of the reactivity is non-selective. This apparent non-selectiveness is a result of specific activity against multiple antigens on target cells by each effector suspension. The specific reactions can be demonstrated through competitive inhibition of natural cell-mediated cytotoxicity. The specific inhibition of cytotoxicity by competitor cells directed our attention toward the determination of specificity to the effector cell surface. Natural cell-mediated cytotoxicity was decreased when effector cells were treated with proteolytic enzymes or low pH and regained when these cells were incubated in serum, suggesting an antibody on cell surfaces of the effector cell. Reconstitution of trypsinized effector cells with absorbed serum resulted in selective loss of cytotoxicity against the absorbing cell. To determine the role of the effector cell and the role of antibodies in natural cell-mediated cytotoxicity, effector cells from two different persons were reconstituted in the same absorbed sera. The selective pattern achieved was similar. When effector cells from the same individual were reconstituted with two different sera absorbed in the same way, the selective pattern achieved showed greater differences. We concluded that natural antibodies loosely attached to effector cells provided the specificity of natural cell-mediated cytotoxicity.

Antibodies↗
PubMed1977

Specificities in natural cell-mediated cytotoxicity by the cross-competition assay.

The cross-competition assay was applied to natural cell-mediated cytotoxicity in human, mouse and rat systems. The results showed that what appeared to be non-selective effects of natural cytotoxicity were in fact highly specific. Each effector suspension included natural effector cells (N cells) that recognized and reacted specifically with many different antigens on target cells, resulting in overall non-selectivity. The specificity of the reaction for each target cell was demonstrated by the selective inhibition of natural cytotoxicity achieved when competitor cells sharing antigens with the target cell were added. Sharing of common target antigens was demonstrated by selective cross-inhibition which was then used to investigate antigens on target cells.

Animals↗
PubMed1977

B cell antigens on effectors for natural cell-mediated cytotoxicity.

Cell suspensions enriched for N cells, the effector cell for human natural cell-mediated cytotoxicity, were observed to react strongly with a rabbit antiserum directed against an antigen associated with B cells. Treatment of the effector suspension with the antiserum resulted in inhibition of natural cell-mediated cytotoxicity. The blocking occurred, however, only with the intact antibody indicating that inhibition was caused through the formation of antigen-antibody complexes. The antiserum was then employed to arm natural effector cells to react specifically with B cell lines. Specific arming was achieved after the formation of antigen-antibody complexes was prevented by initially reacting the effector suspension with F(ab')2 of the anti-B cell antibody. This study also supports the identity of the subset of cells responsible for antibody-dependent and natural cell-mediated cytotoxicity and the similarity in their mechanisms.

Antigen-Antibody Complex↗
PubMed1977

Reconstitution of natural cell-mediated cytotoxicity with specific antibodies.

The apparent nonselective reactions of natural cell-mediated cytotoxicity (NCMC) are selective when tested by inhibition of cytotoxicity with competitor cells indicating a recognition of specificities by the effector cell. N cells that mediate this NCMC in humans have most of the characteristics of K cells that mediate antibody-dependent, cell-mediated cytotoxicity (ADCC) and possess Fc receptors. IgG antibodies attached loosely to N cells through their Fc region, form part of the class of lymphocytes with surface immunoglobulin. We hypothesized that ADCC and NCMS involved similar mechanisms but with the specificity of NCMC directed by the natural IgG antibodies already attached to N cells. Removal of the antibodies with trypsin and reconstitution with specific anti-HLA antibodies produced specific effector cells supporting the role of antibodies on N cells as directors of specificity in NCMC.

Antibody Specificity↗
PubMed1977

Specificities in human cell-mediated cytotoxicity.

Specificity of natural cell-mediated cytotoxicity was investigated through selective reactions detected by direct cell-mediated cytotoxicity and by inhibition of cytotoxicity through competition. Assuming that target cells reacting alike in direct cytotoxicity shared common antigens, we classified 10 target cells into three groups by target antigens: TA (target antigen) 1, 2, and 3. Partial confirmation of the three groups was achieved in the cross-competition assay. The distinction of TA 1 as a group was clear but some cross-reactivity existed between TA 2 and TA 3 cells.

Antigens, Neoplasm↗
PubMed1977

Determination of specificity in natural cell-mediated cytotoxicity by natural antibodies.

Natural cell-mediated cytotoxicity (NCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) appeared to involve similar cytotoxic mechanisms; effector N-cells killed target cells with IgG antibodies attached to the Fc receptor determining the specificity of the reaction. In NCMC the wide range of specificities detected by natural antibodies provided an effector system capable of recognizing numerous antigens on cultured target cells. When several target cells were tested concurrently, an apparent nonselective cytotoxicity resulted. The specificity of individual reactions against each of the target cells could be demonstrated by selective inhibition with competitor cells. The inhibition of cytotoxicity by competition and the effect of proteases on the effector cell for NCMC, but not for ADCC, initially suggested an antibody on the surface of the natural cytotoxic effector cell. This suggestion was supported by the loss of activity with treatments that removed immunoglobulins on the effector cell and by the recovery of reactivity with incubation of the cells in normal human serum. Absorption of the reconstituting serum with target cells resulted in loss of activity against that target cell, substantiating the role of natural antibodies.

Antibodies↗
PubMed1977

Selective reactions in antibody-dependent cell-mediated cytotoxicity.

Selective reactions associated with HLA specificity were sought in antibody-dependent cell-mediated cytotoxic tests against HLA-typed lymphoblastoid lines using operationally monospecific HLA sera and effector cells from healthy individuals. Precise detection of HLA specificities was disturbed by the presence of natural antibodies in HLA antiserum and the effect of the serum and cells on target cell viability. Detection of HLA specificity was improved by absorption of the serum to remove natural antibodies and correction of the results for extraneous cell and serum effects.

Antibodies↗
PubMed1977

Decline of natural nonselective cell-mediated cytotoxicity in patients with tumor progression.

Lymphocytes isolated from the blood of patients and healthy donors include a population of cells that destroy target cells in the direct cell-mediated cytotoxic assay with little indication of specificity. This natural reaction is the dominant feature of most cell-mediated cytotoxic tests and, although it appears to be mostly nonselective, it possesses some selective activity. The observed cytotoxicity from these reactions depends mostly on the reactivity of the effector cell; when several effector cells are tested on different target cells, the relative order of activity is usually maintained on the different target cells. When this natural cytotoxicity was analyzed without regard to the type of cancer of the patient or of the target cells, a weak decline in the average reactivity was observed with increasing tumor involvement.

Adolescent↗
PubMed1976

The nonselective cytotoxic cell (N cell).

When effector lymphocytes were reacted with cultured human tumors, the total cytotoxic reaction could be divided into selective and nonselective components. The nonselective part of the reaction was due to a cell type called N cells. Fractionation of effector suspension indicated that N cells were neither T nor B cells. Like B cells, N cells did not form rosettes with sheep erythrocytes; they were retained by columns coated with lg or antiserum to lg and died preferentially when stored at an ambient temperature. However, N cells were differentiated from B cells by their inability to form complement-receptor rosettes and by their survival when incubated at 30 degrees C. The effect of the nonselective cytotoxic cell must be differentiated from selective activity in studies of specificity for cell-mediated cytotoxicity.

B-Lymphocytes↗
PubMed1976

Interaction analysis of selective and nonselective cell-mediated cytotoxicity.

The coexistence of selective and nonselective cytotoxic cells in effector suspensions required a method of separating the two effects before specificities in cell-mediated cytotoxicity could be investigated. A method of analysis was derived which used the average cytotoxicity for each effector and target to estimate selective and nonselective cytotoxic effects. The analysis clearly detected specificity in tests of cell-mediated lympholysis, and application to tests of cell-mediated cytotoxicity on cultured human tumor cells showed that selective reactions were found.

Cell Separation↗
PubMed1976

Distinct target determinants on two lymphoblastoid lines derived from the same individual1.

Specifically cytotoxic cells were generated in undirectional mixed leukocyte culture against both T and B lymphoblastoid cell lines. The cytotoxicity observed included both specific and less selective components which were differentiated by the interaction analysis based on the two-way analysis of variance. The results indicate that a T cell line and a B cell line derived from the same person possessed distinct target specificities. The antigens detected by direct cytotoxicity were confirmed by inhibition studies with competitor cells.

Cell Line↗
PubMed1975

Autologous stimulation of human lymphocyte subpopulation.

The background stimulation universally seen when lymphocytes are cultured in vitro has been shown to be markedly lowered by reducing the proportion of B lymphocytes. B-rich fractions of lymphocytes had extremely high background stimulation. It is concluded that stimulation of T cells, probably by autologous B cells, provides the most probable explanation for the findings described.

B-Lymphocytes↗