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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spleen dendritic cells (DC) and epidermal Langerhans cells (LC) belong to the same family of dendritic leukocytes and are considered to be prototypes of lymphoid DC and nonlymphoid DC, respectively. These cells are active APC in vitro and play a key role in the induction of primary T cell dependent immune responses in vivo. Two functional states of LC have been characterized in vitro, freshly isolated LC and cultured LC (cLC). That cLC closely resemble spleen DC in phenotype and function, has led to the hypothesis that LC undergo maturation toward DC while in culture, an event that has been correlated with the emigration of LC from skin into lymphoid organs. To date, however, DC have been studied only after overnight culture. To better understand the relationship between LC and DC, we examined DC shortly after their isolation from spleen, and after 24 h of culture. Freshly isolated DC (fDC) express high levels of MHC molecules and low levels of Fc gamma RII and C3biR; fDC also uniformly express the Ag recognized by the mAb 33D1, NLDC-145, and J11d. After culture, DC display a marked increase in the expression of MHC molecules, and they are induced to express the low affinity receptor for IL-2. By contrast, the expression of Fc gamma RII and F4/80 decreases with culture. With respect to function, fDC can efficiently present keyhole limpet hemocyanin to Ag-specific T cells, whereas cultured DC exhibit a marked reduction in this capacity. Finally, both fDC and cultured DC are capable of endocytosing surface Ia molecules, but only fDC are able to deliver them into acidic compartments. Our data indicate that fDC from spleen resemble freshly isolated LC from epidermis and that both cells undergo parallel changes during culture. These results suggest that LC and DC possess analogous attributes in vivo and respond similarly to external influences.
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PMID:Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture. 221 64

Previous reports suggest that immunotherapy can induce T-cell development in athymic nude mice. Eight-week-old BALB/c nu/nu (athymic nude) mice were treated for 3, 6 and 12 weeks with thymosin fraction 5 (TF-5), buffy coat interleukins (BC-IL), recombinant IL-2 (rIL-2), a combination of TF-5 and BC-IL, isoprinosine or imuthiol. Control animals were treated with sterile saline or were given a syngeneic thymus graft. Spleen weight, cell yields and Thy 1.2+ T-cell markers were monitored and spleen cell proliferative responses to rIL-2, concanavalin A (Con A), Con A + rIL-2, phytohemagglutinin (PHA) and endotoxin (LPS) were assessed. Only mice transplanted with a syngeneic thymus showed progressive increases in both T-cell number and function. Minor changes in proliferative responses were noted at 3 weeks with all treatments; however, no biologically significant reconstitution of T-cell number or function was observed.
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PMID:Thymosin, interleukins, isoprinosine and imuthiol do not reconstitute T-cells in athymic nude mice. 246 24

After peroral infection with cysts of Toxoplasma gondii, C57BL/6 mice died and A/J mice survived. To better understand the reasons for this difference in survival, host defenses during acute infection were studied: initial portal of entry of T. gondii contributed to susceptibility as more C57BL/6 mice survived after i.p. than peroral infection (p less than 0.001). Susceptible (C57BL/6) mice had more necrosis and inflammation in their brains, livers, and mesenteric lymph nodes than resistant (A/J) mice. Susceptible mice had less IgM antibody to T. gondii (p less than 0.0005) than resistant mice 7 days after infection, but amounts of IgG antibody to T. gondii were similar. Infection reduced percentages of spleen cells with the Lyt-2+ phenotype in susceptible (p less than 0.02) but not resistant mice; infection decreased percentages of spleen cells with the L3T4+ phenotype similarly in both strains of mice. Spleen cells from infected susceptible mice had greater depression in their blastogenic response to Con A (p less than 0.05) and produced significantly more IFN-gamma in culture with (p = 0.009) or without (p less than 0.05) Toxoplasma Ag than spleen cells from infected resistant mice. Infection increased serum levels of IFN-gamma substantially in susceptible but not resistant mice. Lymphocyte IL-2 production was similar in both groups of mice. Peritoneal macrophages from both strains of mice became activated to inhibit or kill T. gondii by 7 days after infection, but Kupffer cells became activated only in susceptible mice. These results indicate that increased resistance to peroral Toxoplasma infection is likely to be mediated by a number of immune responses acting together. They suggest that increased susceptibility may result from inadequately regulated inflammatory responses that increase tissue destruction.
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PMID:Immune responses associated with early survival after peroral infection with Toxoplasma gondii. 249 63

Lymphocytes of autoimmune mice have been reported to have defective IL-2 production and proliferation in response to the mitogen concanavalin A. We have examined transcription of lymphokine genes in Con A stimulated spleen cells from both autoimmune and normal mice and found that IL-2, IL-4 and gamma-interferon (IFN gamma) were induced in all mice tested. Spleen cells were taken from young (pre-disease) or old (clinically active) MRL/lpr (lpr) and male BXSB autoimmune mice and from their normal counterparts (MRL/n, BXSB females, BALB/c and DBA/2) and stimulated with Con A. Con A induced production of IL-2, IL-4 and IFN gamma message and protein, and kinetics of induction did not vary significantly among the strains. However, in old lpr mice, levels of IL-2 protein and mRNA were about 10-fold lower than in other strains; IL-4 protein and mRNA were decreased approximately three-fold; and IFN gamma mRNA was readily detected in unstimulated cells and low but detectable levels of protein were produced constitutively. In contrast, little or no defect in IL-2 or IL-4 transcription or secretion were seen in male BXSB mice and no constitutive IFN gamma transcription was seen in this strain. These data indicate that all three lymphokine genes are activated by Con A in autoimmune mice, even though Con A-induced proliferation is defective in these mice. Furthermore, autoimmune mouse strains vary in terms of lymphokine expression: male BXSB mice display a normal lymphokine profile, whereas lpr mice show a marked imbalance of lymphokines compared to normal controls.
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PMID:Expression of lymphokine genes in splenic lymphocytes of autoimmune mice. 250 45

Spleen cells from rats that have recovered from experimental autoimmune encephalomyelitis (EAE) suppress the production of IFN-gamma by effector T cells of EAE in an Ag-specific manner. These postrecovery suppressor cells also inhibit EAE in vivo. Fractionation of the postrecovery suppressor spleen cells on nylon wool and OX-8 coated plates yields a nylon wool-adherent CD4+ suppressor cell population that, when cocultured with effector T cells, suppresses IFN-gamma production by these effector cells. In contrast, the nylon wool-adherent, CD4+ postrecovery suppressor cell population fails to inhibit the production of IL-2 by the effector T cells. In further experiments, the effector T cell population was depleted of CD8+ cells and cocultured with the nylon wool-adherent, CD4+ postrecovery suppressor cells, and the supernatants were assayed for IFN-gamma and IL-2. IFN-gamma production was inhibited in these cultures but IL-2 production was not inhibited. Irradiated effector T cells were cocultured with CD4+ postrecovery suppressor cells, without myelin basic protein, in an effort to determine whether the mechanism of differential lymphokine suppression involved an anti-idiotypic response against effector T cells. No IL-2 was produced, indicating that there was no CD4+ suppressor cell mediated anti-idiotypic response against effector T cells. These studies suggest that the suppressor cell is a nylon wool adherent, CD4+ T cell that functions to down-regulate EAE effector T cells by differential inhibition of lymphokine production.
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PMID:CD4+ suppressor cells differentially affect the production of IFN-gamma by effector cells of experimental autoimmune encephalomyelitis. 257 35

Lymphoid cells from mice immunized i.v. or s.c. with Leishmania major antigens were analyzed for their capacity to produce lymphokines when stimulated with specific antigens in vitro. Spleen cells from BALB/c mice immunized by the s.c. route produced significantly higher levels of IL-3 and IL-3 mRNA than those from mice immunized by the i.v. route. The differential production of IL-3 was maintained at a wide range of antigen concentrations tested in vitro and for different culturing times. T cell enrichment procedures and treatment with CD4+ mAb in vitro confirmed the T cell nature of the IL-3 producer population. However, the IL-3 production in the two populations of spleen cells was equally high after Con A stimulation in vitro. The IL-2 production by the two populations of cells was also not significantly different after antigen or mitogen stimulation in vitro. To our knowledge, this is the first report of a differential synthesis of IL-3 mRNA and secretion of IL-3 induced by different routes of immunization followed by specific-antigen stimulation in vitro. These findings may also explain earlier observations that i.v. immunization with leishmanial antigen induces protection, whereas s.c. immunization leads to exacerbation of L. major infection, since IL-3 has been previously shown to promote leishmanial infection. The fact that the phenomenon also extends to other antigen systems suggests that this finding may have a broader implication in immune regulation and vaccine development.
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PMID:Distinct IL-3 activation profile induced by intravenous versus subcutaneous routes of immunization. 278 14

The effects of exogenously administered human recombinant IL-2 (hrIL-2) on resistance to Listeria monocytogenes infection were examined. Intravenous injection of hrIL-2 significantly enhanced antibacterial resistance in both BDF1 and C3H/HeJ mice. The beneficial effect of hrIL-2 was observed with as little as 0.6 micrograms per mouse, whereas optimum protection occurred at 6 micrograms per mouse, hrIL-2 was equally protective when administered concomitant with the listeriae or up to 24 h prior to infection; it had little effect if given after the bacterial challenge. Kinetic experiments indicated that both the peak bacterial burden and the time lag before L. monocytogenes began to be cleared from the spleen and liver were reduced in hrIL-2-treated mice as compared with control mice. Histopathological examination of spleens and livers confirmed that hrIL-2-treated Listeria-infected mice experienced considerably less damage to these organs than did control mice. Spleen cells from Listeria-infected mice exhibited depressed levels of mitogen-induced proliferation coincident with the peak bacterial burden in the spleen and liver and during the subsequent recovery from the infection. Administration of hrIL-2 to uninfected mice had no effect on spleen cell proliferation in response to mitogens in vitro, nor did hrIL-2 treatment restore normal levels of splenocyte proliferative responses to Listeria-infected mice. In addition, hrIL-2 treatment resulted in attenuated levels of serum colony-stimulating activity in infected mice as compared with control infected mice. Coadministration of both hrIL-2 and human recombinant interleukin-1 alpha at various dose and time combinations had no detectable additive or synergistic effect. Although these data do not suggest an obvious mechanism of action, they clearly demonstrate that hrIL-2 can augment host defense against the facultative intracellular pathogen L. monocytogenes.
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PMID:Treatment of mice with human recombinant interleukin-2 augments resistance to the facultative intracellular pathogen Listeria monocytogenes. 278 91

The pharmacokinetics and biodistribution of radioiodinated recombinant interleukin-2 (125I-IL-2) was studied after either intravenous (i.v.) or intraperitoneal (i.p.) injection into C57BL/6 mice. Beta-lactoglobulin radiolabeled with 131I served as a control protein. After i.v. injection, 125I-IL-2 preferentially accumulated in the liver and spleen. Liver accumulation was fast, peaking at 5 min, and was followed by rapid clearance. Spleen accumulation was slightly slower, peaking at 15 min. Blood values 1 min after i.v. injection were 22-34% of the injected doses (I.D.)/gram. These values declined quickly over the next hour. In contrast, after i.p. administration no organ showed specific uptake of 125I-IL-2. Blood values after i.p. injection were essentially constant over 3 h and were greater and more sustained than after i.v. administration. Kidney values for both 125I-IL-2 and 131I-beta-lactoglobulin, after either i.v. or i.p. injection, indicated that the major route of clearance for both compounds was rapid loss through the kidneys.
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PMID:Biodistribution and pharmacokinetics of recombinant, human 125I-interleukin-2 in mice. 278 99

In previous studies it was found that BALB/c (H-2d) was more susceptible than (BALB/c X A)F1 (H-2d X H-2a) to a tumor bearing multiple mismatched minor histocompatibility antigens, the DBA/2 (H-2d) mastocytoma P815, and that this resistance was H-2 linked. In the present studies the immunologic basis of this effect was examined by comparing the cytotoxic-T-lymphocyte (CTL) responses of BALB/c with those of (BALB/c X A)F1. Despite the BALB/c X A)F1's 34-fold greater resistance to P815 in vivo, the numbers of effector cell precursors were found to be similar in the two hosts as shown by (a) similar anti-P815 CTL responses in vitro with T-cell growth factor, (b) similar secondary anti-DBA/2 MiHA responses after in vivo priming with irradiated P815, and (c) similar frequencies of anti-DBA/2 CTL precursors by limiting-dilution analysis. However, priming with proliferating P815 in vivo revealed a defect in the BALB/c animals: Spleen cells from such animals were unable to control the growth of contaminating P815 cells in vitro or to mount strong secondary CTL responses to DBA/2 antigens. The defective priming of BALB/c could be corrected when DBA/2 spleen cells were added to the P815 inoculum. This impaired priming by living tumor cells was not seen in (BALB/c X A)F1. It is concluded that the use of living P815 tumor cells revealed a defect in immunoregulation in BALB/c mice, which rendered them susceptible to tumor growth in spite of apparently adequate numbers of anti-minor-CTL precursors. How the additional H-2 products expressed in the (BALB/c X A)F1 might correct this defect is discussed.
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PMID:Differential resistance to growth of a tumor expressing incompatible minor alloantigens reflects regulatory influences rather than differences in anti-minor-CTL-P frequencies. 285 96

Spleen cells from mice treated with LS2616 display a highly increased response to the polyclonal T cell lectin ConA. The total number of splenic T cells, and the relative ratios between L3T4+ and Lyt-2+ T cells were not altered by LS2616 treatment. By dissecting the overall ConA response it was found that the number of ConA-inducible, IL-2 reactive T cells was unaffected, while ConA-induced IL-2 production was enhanced after LS2616 treatment. Spleen cells from LS2616 treated mice, depleted of G10 adherent macrophages (M phi) and reconstituted with M phi from untreated mice displayed normal levels of ConA responses. M phi depleted spleen cells from untreated animals, cocultured with M phi enriched populations from LS2616 treated animals resulted in an increased ConA response. Furthermore, spleen cells from treated mice were found to be excellent stimulators for alloantigen-induced T cell responses; when used as responders in MLC, however, these cells were comparable to responders from non-treated animals. Taken together the results demonstrate that LS2616 exerts an immunostimulatory effect on M phi, which indirectly facilitates polyclonal and antigen-specific T cell responses. The possible implications of this observation on various immunoregulatory events are discussed.
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PMID:Mechanism of action of the new immunomodulator LS2616 on T cell responses. 295 30


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