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Biomedical subjects

S Kasakura

Publications and source records attributed to S Kasakura.

At least 73 records · Page 4Linked to original sources
PubMed1984

A mitogenic factor, released by stimulated human mononuclear cells and distinct from interleukin 2 (IL 2), B cell growth factor (BCGF), and interleukin 1 (IL 1).

Two lymphocyte mitogenic factors, interleukin 2 (IL 2) and blastogenic factor (BF), are generated concomitantly in human mixed lymphocyte cultures (MLC). The latter mitogenic factor is directly mitogenic for unstimulated lymphocytes, whereas the former mitogenic factor acts only on previously activated lymphocytes. Both factors had a m.w. range, as determined by gel filtration, of 18,000 to 30,000. Thus, these two factors were inseparable on the basis of m.w. size. However, BF and IL 2 were separable during ion exchange chromatography on the DEAE cellulose and phenyl-Sepharose chromatography. In addition, BF activity in the supernatants of MLC reached a maximum after day 5, whereas IL 2 activity peaked at day 3, thus distinguishing BF from IL 2 kinetically. These results clearly indicate that BF activity is mediated by molecules distinct from IL 2. The biochemical relationship between B cell growth factor (BCGF) and BF was also examined. Because BF was readily separable from BCGF by Con A-Sepharose chromatography, BF is distinguishable from BCGF. No augmentation of PHA-stimulated C3H mouse thymocyte proliferation was associated with the preparation of partially purified BF, demonstrating that BF and IL 1 are distinct molecules. Taken together, these results indicate that BF is clearly distinct from IL 2, BCGF, and IL 1. BF-containing MLC supernatants have direct mitogenic activity on both T and B cells. Both T and B cell blastogenic activities copurified during ammonium sulfate precipitation, gel filtration, DEAE cellulose ion exchange chromatography, and hydrophobic chromatography. Thus, these two activities appear to be biochemically inseparable. Monoclonal anti-Tac, that has been suggested to recognize the receptor for human IL 2, was highly inhibitory to the T cell response to the phenyl-Sepharose preparations of BF (IL 2-free). In contrast, this antibody had minimal or no effect on BF-induced B cell proliferation. However, when MLC supernatants were absorbed with a cloned IL 2-dependent T cell line, only IL 2 activity, but not BF activity, was removed, demonstrating that BF and IL 2 have different binding specificities. The precise mechanism(s) by which anti-Tac inhibits BF-induced proliferation of T cells is unknown at present. Additionally, during the course of these experiments, we observed that Con A-Sepharose chromatography could be used as a simple one-step method of separating BCGF from IL 2.

Animals↗
PubMed1983

Suppressor cell induction factor: a new mediator released by stimulated human lymphocytes and distinct from previously described lymphokines.

Suppressor cell induction factor (SIF) was produced by alloantigen-stimulated human peripheral blood lymphocytes, and it activated human T cells to become effective suppressors of the mixed lymphocyte reaction (MLR). The activity of SIF was resistant to 56 degrees C and to pH 2, and was precipitated by 50 to 80% saturated ammonium sulfate. SIF had a m.w. range, as determined by gel filtration, of 18,000 to 29,000; it did not bind to DEAE cellulose columns; and it was recovered in the pH range from 6.9 to 7.3 on isoelectric focusing. SIF was biochemically separable from IL 2, BF, IFN-gamma, and CSF. Furthermore, IL 2 activity was completely removed by absorption of MLC supernatants by murine cytotoxic T lymphocyte line (CTLL) cells, whereas SIF activity was unabsorbable, thus distinguishing SIF from IL 2. In addition, antiviral activity of MLC supernatants was completely abolished by anti-human IFN-gamma serum, whereas SIF activity was unaffected by this antiserum, thus distinguishing SIF from IFN-gamma. Since treatment of these supernatants with antiserum against human lymphoblastoid cell IFN(alpha/beta) had no effect on either antiviral or SIF activities in these supernatants, SIF was also distinguishable from IFN alpha/beta. These results indicate that SIF is a distinct new lymphokine with the ability to induce suppressor function in human T cells.

Colony-Stimulating Factors↗
PubMed1983

A new mediator (suppressor cell induction factor) activating T cell-mediated suppression: characterization of suppressor cells, kinetics of their generation, and mechanism of their action.

Human T cells precultured in MLC supernatant (SIF) could suppress responder cells in MLC. SIF-activated cells expressed suppressor effects equally on both autologous and allogeneic responder cells in MLC. The suppression observed was not due to cell crowding, cell death, depletion of nutrients, absorption of IL 2, alternation in the kinetics of MLC response, production of soluble inhibitory factor, or generation of cytotoxic cells. In this system, suppressor cells were generated after 5 days of culture, and Ia-positive cells were required in the induction of suppressor cells. Suppressor cells themselves, however, were characterized as Ia-negative subsets of T cells; they could be derived from both Fc-IgG receptor-positive and -negative subsets of T cells. Suppressor activity of SIF-treated cells on the MLC response was sensitive to mitomycin C treatment. They apparently exerted their suppressor effect on some early phase of the MLC response. This early event was almost complete within 48 hr after the initiation of MLC. The possibility that SIF may be involved in T-T interactions required in the generation of effective suppression is discussed.

Animals↗
PubMed1978

Cell types involved in cytotoxicity induced by heated cells and inhibition of this cytotoxicity by anti-human B cell sera.

We have studied the induction of cytotoxic activity in human peripheral blood lymphocytes by heated allogeneic cells. By separating T and B cells from the responder and stimulator cell populations we found that cytotoxic cells are generated in responder T cell populations by both T and the B stimulator cells. Rabbit antisera to a membrane glycoprotein complex (33,000 and 27,000 m.w. by SDS-gel electrophoresis) isolated from a human B cell line were utilized to explore further the nature of the effector cells in this type of cytotoxicity. This antiserum, present during the 6-day-culture period, blocked generation of cytotoxic effector cells. Depletion of cells bearing the B cell antigen from the responder cell population by anti-B cell serum and complement (C) eliminated cytotoxicity. Furthermore, heated cell-induced cytotoxicity was blocked by simply pretreating the responder or the stimulator cell populations with anti-B cell serum in the absence of C. Apparently the human lymphocyte that functions as the effector cell in heated cell-induced cytotoxicity bears the Ia-like antigen that might be important in triggering this type of cytotoxicity.

Antilymphocyte Serum↗
PubMed1978

Effect of rabbit anti-human B-cell antigens on the response of lymphocytes stimulated by blastogenic factor.

It has been shown that specific antisera to B-cell determinants can block stimulation in the human mixed lymphocyte reaction. Therefore, it is of interest to study the effect of anti-human B-cell serum on blastogenic activities of the cell-free culture medium (CFM) derived from cultures of human blood lymphocytes. B-cell antigen was prepared from human B-cell line as a glycoprotein complex of mol. wt 27,000 and 33,000. Rabbit antisera to the B-cell antigen after absorption with human platelets or T-cell line (MOLT 4) was shown to react only against B cells but not T cells. The antisera suppressed human mixed lymphocyte reaction but did not affect the response of lymphocytes to PHA. The proliferative response of T-cell enriched population induced by blastogenic factor from lyphocyte cultures was markedly suppressed by the antisera. The inhibited reactivity irrespective of the source (autologous, allogeneic, mixed, T or B cells) of CFM. This is compatible with an effect caused by their interactions with the responding cell rather than blastogenic factor in the CFM. The results of the kinetic experiments suggest that addition of the antiserum at intervals after initiation of the culture only prevents the CFM stimulation of the responder cells that have not yet become committed to divide.

Antigens, Surface↗
PubMed1977

Cytotoxic lymphocytes induced by soluble factors derived from the medium of leukocyte cultures.

Studies were undertaken to evaluate the cytotoxic capacity of human peripheral blood lymphocytes activated by either supernatants (CFM) derived from lymphocyte cultures or lymphocytes treated for 60 min at 45 degrees C. The effect of the addition of heat-treated cells on the cytotoxic activity of CFM-induced effector cells was also studied. CFM from either unmixed or mixed cultures of lymphocytes was capable of activating cytotoxic effector cells. These effector cells could kill any allogeneic target cells but failed to effect cytotoxicity on the target cells autologous to the responding cells. Both the heat-treated cells and CFM from cultures of these cells also activated lymphocytes to cytotoxic effector cells having specific receptors for nonself antigens. The question of whether heat-treated cells activate cytotoxic cells by themselves or through secreted soluble factor cannot yet be clearly answered. The findings of the present investigation suggest that expression of cytotoxicity induced in MLC is not necessarily restricted to the target cells syngeneic to the stimulator cells, but can be extended to any allogeneic target cells by the indirect effect of soluble factor secreted from stimulated cells that causes a polyclonal activation of cytotoxic precursors in the responding cell populations. The present findings also emphasize the need for caution in the use of heat-treated lymphocytes as innocent-bystander cells in MLC to provide additional cytotoxic specificities in the responder cells, since heat-treated cells alone can activate lymphocytes to cytotoxic effector cells that kill any allogeneic target cells.

Cytotoxicity Tests, Immunologic↗
PubMed1977

Blastogenic factors: production by T and B lymphocytes. Effect on T and B cells.

The aim of the present report is to identify the cells responsible for the in vitro production of blastogenic factor and to evaluate the effect of blastogenic factor on T and B lymphocytes. Human T lymphocytes were purified by a nylon wool column filtration method and B-cell-enriched populations were purified by sedimentation of E rosettes on Ficoll-Hypaque. The results were summarized as follows: Both T cells and B cells can produce blastogenic factor. However, blastogenic factor produced by T cells differed in some respects from blastogenic factor produced by B cells. (a) Blastogenic factor produced in unmixed B-cell cultures stimulated both B cells and T cells to proliferate, whereas blastogenic factor produced in unmixed T-cell cultures stimulated only B cells. (b) The production of T-cell blastogenic factor was accelerated when stimulated by allogeneic cells. In contrast, the blastogenic activity of supernatants from mixed cultures of B cells was not different from that of supernatants from unmixed cultures. The significance of these findings for mixed leucocyte reaction is discussed.

B-Lymphocytes↗
PubMed1975

MLC stimulatory capacity and production of blastogenic factor in patients with chronic lymphatic leukemia and Hodgkin's disease.

The aim of the present study is to evaluate the stimulatory capacity of chronic lymphatic leukemia (CLL) and Hodgkin's disease (HD) lymphocytes in the one-way mixed lymphocyte reaction (MLR) and to investigate whether, in patients with these diseases, a correlation exists between the degree of stimulatory capacity and production of a blastogenic factor. These studies might help to resolve the controversy about the nature of the stimulating cells and to offer some insight into the mechanism of the stimulation in the MLR. The significant observations from this study are summarized as follows: (1) Stimulatory capacity of CLL lymphocytes was intact or increased, while their responding capacity was markedly depressed. (2) In our group of patients with advanced Hodgkin's disease, both stimulating and responding capacities were imparied. (3) In these patients a correlation existed between the degree of stimulatory capacity and production of a blastogenic factor. This observation would raise the possibility that the production of a blostogenic factor may in some way be involved in the stimulation of responding lymphocytes in mixed cultures. Our results, which show a dichotomy between MLC stimulatory and responding capacities of CLL lymphocyte, may suggest that different factors are involved in stimulation and response.

Hodgkin Disease↗