Kazuto Taniguchi

Antitumor effect induced by a hot water extract of Chlorella vulgaris (CE): Resistance to meth-A tumor growth mediated by CE-induced polymorphonuclear leukocytes

SummaryWhen a hot water extract of Chlorella vulgaris (CE) was injected into the peritoneal cavity of BALB/c mice inoculated with syngeneic Meth-A tumor cells, the survival times were strikingly prolonged. Furthermore, peritoneal exudate cells (PEC) rich in polymorphonuclear cells (PMN) obtained from normal mice 24 h after CE injection exhibited an antitumor effect in a Winn-type assay using normal recipients. Such an activity of PEC remained almost intact after T cell or macrophage depletion. However, such PEC did not express an antitumor effect in a Winn-type assay using irradiated recipients. It was suggested that CE-induced PEC, presumably PMN, expressed an antitumor effect in cooperation with a host- or recipient-derived element(s) sensitive to irradiation. The anti-tumor mechanism of CE may be different from that of OK-432, one of the biological response modifiers.

Augmentation of antitumor resistance by a strain of unicellular green algae, Chlorella vulgaris

SummaryGrowth of Meth-A tumor in CDF1 mice was inhibited significantly by injection of a hot water extract of a strain of Chlorella vulgaris (CE) into the tumor or into the subcutaneous tissue near the tumor. The augmentation of resistance by CE may require the participation of T cells and macrophages, since it was abolished or reduced in athymic nude mice or mice treated with carrageenan, a macrophage blocker. Mice treated with CE exhibited antigen-specific augmented resistance against rechallenge with tumor. Moreover, the antitumor effect of CE was comparable with that of Corynebacterium parvum, but its mechanism of effect might be different.

Thymus-dependent increases in splenic T-cell population by indomethacin

After administration of indomethacin, an inhibitor of prostaglandin synthesis, the number of splenic T cells increased in normal mice but not in adult-thymectomized or athymic nude mice. The enlarged T-cell population consisted mainly of Lyt-1+2+ cells. This thymus-dependent increase in T-cell population augmented in vivo antibody response to sheep erythrocytes, a T-dependent antigen. The increased T-cell population also included suppressor cells that were eliminated by treatment with anti-Lyt-2 antibody plus complement. These results suggest that increased T cells in the spleen were recruited from the thymus by an indomethacin-mediated mechanism and participated in immune responses as regulator cells.

Positive effects of indomethacin on restoration of splenic nucleated cell populations in mice given sublethal irradiation

Splenic cellularity during the recovery phase after 400-R irradiation was evaluated in mice, in which the level of prostaglandin was regulated by indomethacin and exogenous prostaglandin E2, following sublethal irradiation. Two weeks after irradiation, administration to these mice of indomethacin, an inhibitor of prostaglandin synthesis, augmented the recovery of all nucleated spleen cell populations, whereas the thymus was drastically depopulated. This treatment had little effect upon the total number of bone marrow cells but inversed the ratio of PNA+/PNA- cells. Cell transfer experiments using heavily irradiated mice as recipients showed that the stem cell proliferation was positively affected by indomethacin treatment in the bone marrow rather than in the spleen. These results suggest that cell migration from primary lymphoid organs, particularly from the bone marrow to the spleen, is regulated by a prostaglandin-mediated system and that a prostaglandin E2 synthesis inhibition would have a positive effect on the restoration of peripheral nucleated cells following irradiation.

Inverse relationship in H-2-associated lysis between NK cells and rIL-2-activated killer cells: Evidence from in vitro killing and metastatic experiments

We investigated the manner in which rIL-2 induced effectors in vitro (LAK cells), which, like NK cells, lyse targets nonspecifically and discriminate nonself, and how H-2 as the self-marker affects the LAK cell killing mechanism. NK cells showed an appreciably higher killing activity to B16 melanoma H-2- cells than to H-2+ cells. In contrast, LAK cells lysed more efficiently to H-2+ cells. The in vivo experiments showed that the NK cells prevented pulmonary metastasis of B16 H-2- cells in the normal syngeneic host, whereas the transferred LAK cells had a preferential inhibitory effect on the pulmonary metastasis of B16 H-2+ cells in the immunodeficient syngeneic hosts. Taken together, these results show that the H-2-encoded or H-2-associated molecules contribute to the triggering signal in the lysis by LAK cells, whereas the NK cells recognize the reduced self H-2 expression on the targets, thereby contributing to a trigger of the lysis.

The role of cytostasis in antitumor immunity: Comparison between syngeneic and allogeneic systems

Different aspects of the immune response differ with respect to sensitivity of neonatal thymectomy (NTx). The effect of thymectomy on Days 1 and 7 after birth (NTx-1, NTx-7) on antitumor immune responses to both a syngeneic and an allogeneic tumor graft was examined. The tumor used was the same, Meth A fibrosarcoma of BALB/c origin, but the mice inoculated differed. The results show that the immune response to a syngeneic tumor graft is primarily cytostatic rather than cytolytic and is relatively insensitive to neonatal thymectomy, while the response to a large dose of allogeneic tumor cells includes a cytolytic mechanism of high thymus dependence.

T-Celll Recruitment Regulated by Prostaglandin-mediated System and its Role in Immune Response

The dynamics of the number of T cells in spleen and the level of prostaglandin E2 in plasma were investigated serially in mice injected with Corynebacterium parvum. In the first few days, the level of plasma PGE2 increased but decreased to lower than the normal level thereafter. The absolute number of T cells in the spleen began to increase after the PGE2 level dropped. But such an increase of T cells was not observed in ATx mice challenged with C. parvum. Moreover, replenishing the mice with exogenous PGE2 in the period of low PGE2 halted selectively the increase of T cells in the spleen. This enlarged T cell subset responded to PHA, expressed Lyt-1+2+, and was sensitive to PGE2. And this T-cell subpopulation exerted a suppressive effect on antibody response in low PG environment, but lost its inhibitory effect in high PG milieu. These results suggested that an immature T cell subset is recruited from the thymus in a low PG state and participates as regulator cells in immune response at peripheral lymphoid organs.

T cell recruitment from the thymus to the spleen in tumor-bearing mice. I: Analysis of recruited cells by surface markers

After inoculation of tumor cells (methylcholanthrene-induced sarcoma), the number of Thy 1+ cells and PNA (peanut agglutinin) binding cells, which were shown to be different subpopulations were increased in the spleen of thymus-intact mice, in contrast this increase was not observed in adult thymectomized mice. In experiments performed concurrently with splenic cell analysis, we found that the plasma PGE2 levels declined in parallel with the tumor growth. Prevention of such a decline of plasma PGE2 level by replenishment with exogenous PGE2 inhibited the splenic cell increase in tumor bearers. In the tumor-bearing mice, cell traffic systems from the thymus to the periphery was ascertained by injecting fluorescein diacetate (FDA) into the thymus and observing fluorescein positive cells in the periphery. We suggest that increased recruitment of thymic cells to the periphery may be mediated by PGE2 in the presence of a tumor.

Development of Immunity against Listeria monocytogenes in athymic Nude versus neonatally thymectomized mice

The thymus requirement for the development of immunological responsiveness was determined by estimation of immune responses raised to Listeria monocytogenes in athymic nude, neonatally thymectomized, and sham-operated mice at 6 weeks of age. Not only sham-operated mice, but also neonatally thymectomized mice could completely eliminate the bacteria from the spleen and liver, while athymic nude mice could not eliminate them and showed a persistent form of infection. A strong delayed footpad reaction and acquired cellular resistance could be raised in neonatally thymectomized mice just as well as in sham-operated mice, but not in athymic nude mice. The delayed footpad reaction could be induced in neonatally thymectomized mice without an accompanying ability to inhibit macrophage migration. These results suggest that T cells responsible for immunity against listerial infection require the presence of the thymus for only a very short period in their development.

Thymus cell migration in a prostaglandin-mediated system.

Prostaglandin (PG)-mediated T cell traffic and the nature of these emigrant T cells were analyzed by using a fluorescent activated cell sorter. Administration of indomethacin (INDO), an inhibitor of PG synthesis, increased the number of splenic T cells in normal mice but not in adult-thymectomized mice. An increase in thymus cell migrants in peripheral blood lymphocyte and splenic cell populations of mice pretreated with INDO were detected, using the method of in situ labelling of thymocytes with fluorescein diacetate. These results indicate that the increase in the T cell population in the spleen by INDO treatment results from the increase in thymus cell migration to the spleen. Such recent emigrants in the spleen were thought to have been derived from the thymus cortex, judging from the response to phytohemagglutinin and intracellular terminal deoxynucleotidyl transferase activity; however, they expressed a Thy-1 level similar to that found on peripheral T cells. These results suggested that a cortical thymocyte population was recruited from the thymus to the spleen by a PG-mediated system, but its Thy-1 level rapidly changed to that found on the peripheral T cell population.