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PubMed1981

The presence of a tumour in F1 mice partially inhibits the GvH reaction following injection of parental spleen cells.

(A x CBA(T6)F1 mice bearing F1 mammary carcinomas for 9 days were injected i.v. with A strain spleen cells. The A spleen cells were from either non-immune donors or mice which had received an i.p. injection of F1 tumours cells 9 days previously, and were thus immune to the CBA component of the tumour. Fourteen days after receiving parental spleen cells, the F1-tumour-bearing mice were killed and their spleen ratios and indices were determined as an index of the severity of the graft-versus-host reaction (GvHR) induced. The spleen indices were compared with those in non-tumour-bearing F1 mice, receiving aliquots of the same parental cell suspensions. At the higher doses of A spleen cells, the presence of an F1 tumour reduced the GvHR. At the same time, in 3/5 experiments, the weight of the F1 tumour in mice injected with immune A spleen cells was less than that in F1 mice receiving the same number of tumour cells but no spleen cells. A reduction in GvHR and a decrease in tumour weight was not seen when F1 mice carrying an A strain tumour were injected with A strain spleen cells immune to an F1 tumour. Adding 23-day F1 tumour-bearing F1 spleen cells to A spleen cells did not reduce the GvHR induced in further non-tumour-bearing F1 recipients by the parental cells. This was evidence against the presence of suppressor cells in the tumour-bearing F1 spleen. When 51Cr-labelled A strain spleen cells were injected into F1 mice, some of which had a tumour and therefore an enlarged spleen, there was an inverse relation between the size of the spleen and the number of parental cells therein, per g spleen 4 h after injection. It is thus suggested that the reduction in GvHR in F1-tumour-bearing F1 mice, after injection of parental spleen cells, is due first to a reduction in the concentration of donor cells in the recipient spleen (i.e. the same number of donor cells in a larger spleen) and second to pre-occupation of the donor cells in reacting to the tumour.

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PubMed1990

"Intermediate zone" of mammalian spleens: light and electron microscopic study of three primitive mammalian species (platypus, shrew, and mole) with special reference to intrasplenic arteriovenous communication.

The intermediate zone (IZ) of nonperfused and perfused spleens in three species of primitive mammals (shrew, mole, platypus) was studied morphologically. The IZ is a tissue zone consisting of plexiform vessels, probably venous capillaries, and is located transitionally between the white and red pulp. The IZ is separated from the white pulp by the arterial net (AN), in which the white pulp arteries terminate. Development of the IZ differs between the three species examined being distinctive in the platypus and shrew. The IZ is thin in the mole spleen. A closed type of arteriovenous (A-V) anastomosis was demonstrated in or around the IZ in the two Insectivora species examined. In the shrew spleen, peripheral arterial branches running within the IZ anastomose with the AN around the follicle. The AN anastomoses eventually with venous plexiform vessels of the IZ around the nonfollicular area of the white pulp to form a closed system. In the mole spleen, A-V anastomoses were noted between white pulp arteries (follicular and AN) and veins of the red pulp, either by direct communication or through fenestrated IZ vessels compatible with the plexiform vessels of the shrew spleen. A-V anastomosis in the IZ is probable, but not confirmed, in the platypus spleen, as analysis was limited to a nonperfused specimen. Well-developed ellipsoids were noted around arterial terminals of the IZ in the shrew spleen. Ellipsoids were also noted around all arterial terminals of the mole spleen directed to the red pulp. Most ellipsoids of the mole spleen appeared located within the IZ. No ellipsoids were present around arterial terminals of the IZ in the platypus spleen. Closed circulation was noted in terminals of the pulp artery in spleens of all three species. All pulp arteries of the mole spleen are postellipsoid segments of white pulp (AN and follicle) arteries. No ellipsoids were found around terminals of the pulp artery (penicillar artery) in shrew and platypus spleens. The IZ is probably homologous to the perilymphatic sinusoid (vein) of the lungfish spleen and may be regarded as part of the red pulp. The IZ may be representative of primitive mammalian spleens that have closed circulation. The marginal zone (MZ) of common mammalian spleens is probably a modified IZ by differentiation (remodelling) of the intrasplenic vein. In this process, withdrawal of venous vessels from the IZ occurred, leaving a lymphoreticular zone with open circulation (MZ). The marginal sinus reported in some mammalian spleens is probably a modified AN formed during this process. Possible morphological alterations of the spleen in vertebrate phylogeny are discussed.

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PubMed1982

Differential effector functions of central and peripheral compartments of immune response system: characterization of immune responses in the spleen and mesenteric lymph nodes to directly injected sheep red blood cells.

When sheep red blood cells (SRBC) were injected intraperitoneally (i.p.), intravenously (i.v.), or into the Peyer's patches, definite plaque-forming cell (PFC) and rosette-forming cell (RFC) responses were induced in the spleen but not in the mesenteric lymph nodes (MLN). When SRBC were injected directly into the spleen or MLN, stronger PFC and RFC responses were induced in the spleen or MLN, respectively, than when injected i.p. or i.v. PFC response induced in MLN by injecting SRBC into MLN with or without the polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K) as an immunological adjuvant was weaker than that induced in the spleen by injecting the antigen into the spleen. Direct PFC (PFC of IgM type) and RFC responses induced in the spleen by injecting SRBC into MLN were rather stronger than those induced in the spleen by injecting the antigen into the spleen. In contrast, no significant responses were induced in MLN by injecting SRBC into the spleen, and no definite indirect PFC (PFC of IgG type) response was induced in the spleen by injecting the antigen into MLN. The levels of whole immunological memory as well as isolated B- or T-cell memory in the spleen and MLN of mice injected with SRBC directly into the spleen or MLN were determined by using an in vitro assay system. Definite amounts of either B- or T-cell memory were detected in the spleen of mice injected with SRBC directly into the spleen of MLN. Smaller amounts of memory were detected in MLN injected with SRBC directly into the spleen. Moreover, the amounts of whole memory detected in MLN were much less than compared with those of isolated T- and B-cell memories in MLN. Further experiments showed that in vitro expression of the memories preserved in MLN required supplement of glass non-adherent cells from normal spleen. Based on these results, we discussed the possible differential and collaborative functions of the central (spleen) and peripheral (MLN) immune response systems in antibody responses.

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PubMed1990

Sex hormone modulation of interferon (IFN) alpha/beta and gamma production by mouse spleen cell subsets following picornavirus infection.

Replication of the diabetogenic variant of encephalomyocarditis virus (EMCV-D) in spleen cells and its association with subpopulations of spleen cells (L3T4+, Lyt-2+, Mac 1+, 33D1+ and AGM1+ cells) from both sexes of ICR Swiss mice were examined. Virus replication was limited to less than 0.5 log in suspensions of whole spleen cells, nonadherent cells or a B cell subfraction from both sexes of ICR Swiss mice following infection with EMCV-D at an MOI of 10; no virus replication was seen in adherent spleen cells from either sex. After 1 hour adsorption of EMCV-D onto spleen cells at a multiplicity of infection (MOI) of either 10 or 0.1, virus-associated cells were isolated using a monoclonal murine anti-EMCV-D and anti-mouse IgG conjugated to magnetic beads. Using an MOI of 0.1, less than 1% of spleen cells bound virus particles after 1 hour adsorption at 4 degrees C. Among the virus-positive cells, relatively higher percentages of adherent cell populations (Mac 1+ and 33D1+ cells) of both sexes bound virus particles within the first hour post-infection (PI) than did the other spleen cell subpopulations. Interferon (IFN) alpha/beta production was detected as early as 4 hours PI in female spleen cell cultures infected with EMCV-D at an MOI of 0.1 while no IFN alpha/beta activity was found in comparably infected male spleen cell cultures. Inhibiting IFN alpha/beta activity in the virus-infected spleen cell cultures during the first 20 hours of infection using polyclonal rabbit anti-mouse IFN alpha/beta serum eliminated production of IFN gamma as well as IFN alpha/beta. Spleen cell cultures depleted of adherent cells were unable to produce IFN alpha/beta or IFN gamma in the first 24 hours PI. The capacity to produce IFN gamma at 12 hours after virus infection of spleen cells from both sexes of mice was restored to adherent cell-depleted cultures by addition of mouse IFN alpha/beta at the time of infection. These results suggest that IFN alpha/beta and adherent cells play critical roles in the early production of IFN gamma (less than 16 hours PI) characteristic of the infected spleen cell cultures of females. Production of IFN alpha/beta and IFN gamma by spleen cells from both sexes of ICR Swiss mice was enhanced by administrating estrone to donor mice during the week before harvesting spleen cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1986

Macrophage tumoricidal activity as a possible antitumor mechanism associated with the local injection of allogeneic spleen cells into rats.

The in vivo antitumor effect of i.p. injection of allogeneic spleen cells was investigated. ACl rats were inoculated i.p. with 10(4) AMC-60 syngeneic fibrosarcoma cells and given injections i.p. of 4 X 10(7) Wistar spleen cells once a week for 3 wk from 1 day after tumor inoculation. This treatment significantly prolonged the survival period of the tumor-bearing rats. A similar effect was obtained by i.p. injections of Lewis spleen cells. Injection i.p. into ACl rats of spleen cells of these rat strains resulted in the apparent augmentation of cytolytic activity of peritoneal adherent but not of nonadherent cells against AMC-60 tumor cells. The cytotoxicity was exhibited nonspecifically to cells of a variety of tumor lines but not to concanavalin A blasts of ACl spleen cells and was inhibited by the addition of carrageenan. Irradiation (2000 R) of Lewis spleen cells or fractionation of the allogeneic spleen cells using nylon wool columns revealed that a radiosensitive and nylon wool-passed cell population, presumably a T-cell population, of the allogeneic spleen cells is responsible for the augmentation of peritoneal macrophage tumoricidal activity in ACl rats. Further, Lewis spleen cells irradiated at 2000 R neither augmented peritoneal macrophage cytotoxicity nor prolonged the survival period of ACl rats bearing AMC-60 tumor, suggesting that the augmentation of peritoneal macrophage cytotoxicity plays a major role in the in vivo antitumor effect of the allogeneic spleen cell transfer. ACl rats were given injections i.p. of 4 X 10(7) Lewis spleen cells. Two days after injection, cells including peritoneal cells of the ACl rats and Lewis spleen cells remaining in the peritoneal cavities were obtained by peritoneal lavages and then incubated for 5 days. Significant blastogenic proliferation was observed, and the supernatant of the culture was shown to be able to render thioglycollate-induced peritoneal macrophages of ACl rats cytotoxic to AMC-60 tumor cells, indicating that a certain cell population of the cell mixture produced a lymphokine(s) resembling macrophage activating factor (MAF) during the incubation. When ACl rats were given injections i.p. of irradiated Lewis spleen cells, neither the blastogenic proliferation nor the generation of MAF activity in the culture supernatant was observed. Indirect immunofluorescence analysis using rabbit anti-ACl and anti-Lewis antisera revealed that as many irradiated Lewis spleen cells were remaining in the peritoneal cavities as normal Lewis spleen cells 2 days after injection into ACl rats.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMedDate not supplied

Idiotypic specificities of rabbit anti-Salmonella abortus-equi antibodies produced by spleen cell clones involved in successive transfers in irradiated rabbits.

Rabbits irradiated with 750 rad were reconstituted with different amounts of spleen cells from the same donor previously immunized against Salmonella abortus-equi (S. a. e.). Two limited numbers of spleen cell clones producing anti-S. a. e. antibodies were respectively expressed in two recipients of the smallest amount (5 x 10(6)) of donor spleen cells. We tried to propagate these spleen cell clones in two new sets of irradiated recipients. We prepared antiidiotypic sera with the anti-S. a. e. serum of respectively (1) the initial donor of the cells, (2) the two intermediate recipients in which a restricted number of spleen cell clones were expressed and (3) one rabbit from each of the second two sets of recipients in which it seemed, as judged by the anti-S. a. e. antibody spectrotypes, we succeeded in propagating these spleen cell clones. With these antiidiotypic sera, we looked for the spleen cell donor idiotypes in the anti-S. a. e. serum of the diverse recipients and vice versa. Recipients of 1 x 10(8) or 2.5 x 10(7) spleen cells produced anti-S. a. e. antibodies with a spectrotype as heterogeneous as the spectrotype of antibodies produced by the donor. These antibodies carried the idiotypic pattern of the donor's antibodies, which was revealed by a given antiidiotypic serum, and the donor's allotypic patterns. The two recipients of 5 x 10(6) spleen cells which were used as intermediate spleen cell donors for the two new sets of irradiated rabbits produced antibodies of restricted heterogeneity which carried donor's allotypic patterns but not the idiotypic pattern of the donor's antibodies (revealed by a given antiidiotypic serum). We observed during these two successive spleen cell clone transfers the expression, in the irradiated recipients, of several idiotypes of anti-S. a. e. antibodies which were not detected in the anti-S. a. e. serum of the spleen cell donor and sometimes even not in the anti-S. a. e. serum of the intermediate donor. The antibodies we studied were produced by the donor's spleen cells as they carried donor allotypic patterns and came from bleedings made one week after transfer, a time which is not sufficient for irradiated rabbits used as controls to recover their aptitude to mount an antibody response after the damages caused by the irradiation. Presumably, spleen cell clones which did not produce antibodies in the donor were recruited to produce antibodies during the successive transfers. These spleen cell clones might have been kept silent in the donor by the clonal dominance phenomenon, this dominance being broken or totally changed during the transfers.

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