Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was performed in order to define the responding populations and profiles of cytokine production in BCG-primed spleen cells restimulated in vitro with antigen. Spleen cells from DBA/2 mice, one of BCG-resistant strains (Bcgr), infected with Mycobacterium bovis BCG vigorously proliferated by restimulation with heat-killed BCG. This response peaked as early as on day 3 after BCG infection, and then decreased to the basal level by 3 weeks. Blocking of IL-2R alpha chain or IL-4 by each antibody partially inhibited it, but anti-IFN-gamma antibody did not, suggesting that both IL-2 and IL-4 were involved in the proliferation of primed spleen cells. CD4+ and gamma delta TCR-bearing T cell were responding populations to BCG, but CD8+ T cell was not, because depletion of CD4+ or gamma delta T cells by the treatment with each antibody and complement inhibited proliferation and IL-2/IL-4 production, but that of CD8+ T cells did not. Further study demonstrated that spleen cells from BCG-resistant DBA/2 mice produced more IL-2/IL-4 than those from BALB/c mice, one of BCG-susceptible strains (Bcgs), in response to BCG. These results suggest that both CD4+ and gamma delta TCR-bearing T cells play an important role in the host defense against M. bovis BCG infection, and that the magnitude of cytokine production is one of the critical factors to define the susceptibility of mice to this pathogen in the late phase of infection.
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PMID:[Analysis of antigen-specific proliferation and IL-2/IL-4 production of spleen cells from mice infected with Mycobacterium bovis BCG]. 776 May 38

The gene encoding for a major surface glycoprotein, gp63, of Leishmania major was cloned into the eukaryotic expression plasmid pCDNAI with CMV or RSV promoters. The highly susceptible Balb/c mice were injected intramuscularly with 100 micrograms/mouse of the purified plasmid. The plasmids were found to be stable in vivo for at least 40 days after injection and expressed significant levels of gp63, demonstrable by immunohistological staining with specific antibody. The immunized mice developed significant resistance against L. major infection compared to controls similarly immunized with the empty plasmid. Spleen cells from the immunized mice produced significant levels of IL-2 and IFN-gamma but no detectable IL-4 when cultured with leishmanial antigens in vitro.
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PMID:Genetic vaccination against leishmaniasis. 787 20

We investigated whether the responsiveness of anti-tumor CD4+ T cells suppressed in the tumor-bearing state is reversed in conditions free of tumor burden. Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1-3 wk after inoculation with CSA1M cells produced interleukin-2 (IL-2) and IL-4 upon in vitro culture without addition of exogenous tumor antigens. This lymphokine production was achieved through collaboration between anti-CSA1M CD4+ T cells and antigen-presenting cells (APC) that had been pulsed with CSA1M tumor antigens in vivo in the tumor-bearing state. However, spleen cells from late (8-10 wk) tumor-bearing stages produced reduced levels of lymphokine production despite the presence of comparable proportions of CD4+ T cells. Because APC in these cell populations exhibited enhanced capacities to present tumor antigens, reduced responsiveness was ascribed to the dysfunction of CD4+ T cells themselves. When spleen cells from early tumor-bearing mice were preincubated for 1-2 days and recultured in fresh medium, the magnitude of lymphokine production by these cells was not changed. In contrast, the same protocol of preincubation and reculture for cells from late tumor-bearing mice resulted in the recovery of anti-tumor lymphokine-producing capacity. The recovered capacity was comparable to or slightly higher than that expressed by cells from early tumor-bearing stages. Since the CD4+ T cell content did not significantly differ before and after preincubation, enhanced lymphokine production was due to the recovered responsiveness of anti-tumor CD4+ helper T cells. The recovery of anti-tumor responsiveness was also induced in vivo by tumor removal at the late tumor-bearing stage: spleen cells from mice 2-4 wk after tumor resection efficiently produced IL-2 and IL-4. These results indicate that the immunodysfunction of anti-tumor CD4+ T cells induced in the tumor-bearing state is reversible because release from tumor burden either by preincubation in vitro or by tumor removal in vivo results in almost complete recovery of the potent anti-tumor responsiveness initially expressed.
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PMID:Suppression of anti-tumor CD4+ T cell responsiveness in the tumor-bearing state and its recovery in in vitro culture free of tumor burden. 790 64

The present study investigates the recovery of antitumor CD4+ T cell responsiveness, suppressed in the tumor-bearing state, following release of tumor burden. Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1-3 weeks after the inoculation with CSA1M cells produced interleukin-2 (IL-2) and IL-4 upon in vitro cultures without addition of exogenous tumor antigens. This lymphokine production was achieved through collaboration between anti-CSA1M CD4+ T cells and antigen-presenting cells (APC) that has been pulsed with CSA1M tumor antigens in vivo in the tumor-bearing state. The lymphokine-producing capacity gradually decreased as the tumor-bearing period increased, and spleen cells from mice at late (8-10 week) tumor-bearing stages produced reduced levels of lymphokines. Because APC in these cells exhibited enhanced capacities to present tumor antigens, the reduced responsiveness was ascribed to the dysfunction of CD4+ T cells themselves. However, removal of a tumor after 8 weeks resulted in a remarkable recovery of the lymphokine-producing capacities of whole spleen cells. In contrast to the reduction in CSA1M-antigen-presenting activity of APC following tumor resection, CD4+ T cells exhibited a reciprocal increase in their responsiveness to CSA1M antigens. The recovery of antitumor responsiveness was also observed in the in vitro cultures free from tumor burden; when spleen cells from mice at late tumor-bearing stages were pre-incubated for 1-2 days and re-cultured in fresh medium, they produced potent amounts of IL-2 and IL-4. These results indicate that the immunodysfunction of antitumor CD4+ T cells induced in the tumor-bearing state is not irreversible, and release from tumor burden results in almost complete recovery of the potent antitumor responsiveness they previously expressed.
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PMID:Recovery of antitumor CD4+ T cell responsiveness, suppressed in the tumor-bearing state, by release from tumor burden. 790 34

Salivary gland extract (SGE) of the blood-feeding black fly Simulium vittatum is known to modulate immunological responses. In the present study, the ability of S. vittatum SGE to modulate responses during heterologous antigenic challenge was investigated in a murine model, with particular emphasis on characterizing the patterns of cytokine response. Mice were injected repeatedly with SGE or saline (sham), then challenged with the T dependent antigen ovalbumin (OVA) to generate antigen-specific lymphoblasts. Spleen cells from OVA-primed mice were then co-cultured with OVA in vitro to stimulate cytokine secretion. Cells from mice that had been injected with SGE prior to OVA challenge produced lower levels of interleukins 5 and 10 (IL-5 and IL-10) in in vitro culture, when stimulated with OVA, compared to mice that had been sham-injected with saline. Levels of IFN-gamma, IL-2 and IL-4 did not differ significantly between SGE- and saline-injected groups. Mice injected repeatedly with SGE prior to OVA challenge had fewer circulating eosinophils than sham-injected mice, while other leukocyte levels were unaffected by SGE. Prior exposure to SGE did not affect levels of serum IgE or IgA significantly. The effect of SGE on the ability of murine spleen cells to respond in vitro to the recombinant cytokines IL-2 and IL-4 was also investigated. Naive spleen cells pre-incubated with SGE proliferated less in response to both IL-2 and IL-4 in in vitro culture than cells pre-incubated with saline as a control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of murine cellular immune responses and cytokines by salivary gland extract of the black fly Simulium vittatum. 793 61

The BALB/c mouse immunized sub-cutaneously (s.c.) with 45 kRad attenuated third stage larvae (L3) of the lymphatic filarial nematode Brugia pahangi is strongly immune to a challenge infection (75-100% reduction in recovery at day six post challenge). Analysis of spleen cell supernatants from immunized mice re-stimulated in vitro, with parasite antigen or the non specific T cell mitogen Con-A reveals a cytokine profile (IL-4, IL-5 and IL-9) which indicates that the Th2 subset of CD4 cells has been expanded. In an attempt to formally prove a critical role for CD4 cells in immunity in this model system, immunized mice were given either anti-CD4 or anti-CD8 neutralizing antibodies. Administration of anti-CD4 antibody had a significant and detrimental effect on the immune response whereas anti-CD8 antibody had a negligible effect on immunity. The efficacy of antibody in neutralizing their target cells was determined by fluorescence activated cell sorting analysis (FACS). Spleen cells from anti-CD4 treated immunized mice, when re-stimulated with parasite antigen had a significantly reduced potential to secrete IL-4, IL-5 and IL-9 in vitro and serum from these mice had reduced levels of parasite specific IgG and IgE. These results demonstrate a critical role for CD4 T cells in host protective immunity to B. pahangi in vivo and strongly suggest that some component of the Th2 response plays an important role in the immune response elicited in this model system.
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PMID:The role of CD4 cells in protective immunity to Brugia pahangi. 797 Aug 77

The oral administration of CII by gavage to WA/KIR rats before a conventional arthritogenic challenge with bovine CII in FIA reduced the incidence (by 23%) and delayed the onset of collagen-induced arthritis in about 50% of the animals. Selective changes in B cell and T cell responses to CII in animals treated this way are interpreted to indicate a state of tolerance or hyporesponsiveness to CII. Tolerant animals made less serum antibody, to bovine and rat CII, of the IgG2b isotype and more of the IgG1 isotype. Phenotypic and functional analysis of peripheral lymph node cells showed that those from tolerized animals expressed less MHC Class II, proliferated less and secreted less IgG2b anti-CII antibody in response to stimulation in vitro with CII when compared with cells from non-tolerant animals. However, this depression of the immune responses to CII seen in vitro was overcome when the cells were incubated with increasing amounts of CII. Tolerance could be transferred to normal animals. Spleen cells, and nylon wool-filtered splenic T cells (but not mesenteric lymph node cells) adoptively transferred hyporesponsiveness to normal recipients which were then less susceptible to collagen-induced arthritis. Transfer of serum from gavaged animals did not modify the susceptibility of normal recipients to arthritis. Spleen cells from gavaged animals suppressed proliferative and antibody responses in co-cultures in vitro with lymph node cells from animals immunized with CII in FIA. The suppressive spleen cell population contained more cells expressing MHC Class II, in both the CD8+ and CD4+ populations. These studies show that the oral administration of CII alters the subsequent immune response to the arthritogenic challenge and indicate that this oral tolerance of CII is due, not to clonal deletion or anergy, but rather to an antigen-driven active suppression mechanism that affects both T cells and B cells, most likely through the action of regulatory cytokines IL-4, IL-10 and TGF beta.
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PMID:Suppression of collagen induced arthritis by oral administration of type II collagen: changes in immune and arthritic responses mediated by active peripheral suppression. 800 14

C3H/HeH or C57BL/6 mice were injected with resting or Escherichia coli lipopolysaccharide (LPS)-stimulated splenic B cells from adult B10.BR mice. Animals were grafted with tail skin grafts from B10.BR mice 36 hr later. Spleen cells were removed from these mice 7 days after grafting and challenged in tissue culture with irradiated B10.BR spleen cells or BALB/c cells. LPS blasts, but not naive B cells, induced an antigen-specific reduction in proliferation and IL-2 production from stimulated C3H/HeJ cells. The response obtained from C57BL/6 spleen responder cells was increased by this treatment. IL-4 production was either unchanged (C57BL/6) or enhanced (C3H/HeJ). Modification of the C3H/HeJ anti-B10.BR response by B blasts was not blocked by CTLA-4 Ig, although the increased response seen using MHC-incompatible (C57BL/6) spleen cells was inhibited by CTLA-4 Ig. B10.BR, but not BALB/c, skin graft survival in vivo was enhanced in C3H/HeJ recipients of B10.BR B blasts. In addition, in lymph nodes draining the graft site of C3H/HeJ mice injected with B10.BR LPS blasts, mRNA for IL-4 was detected by polymerase chain reaction. When similar studies were performed with B10.BR immune C3H/HeJ or C57BL/6 mice, no enhancement of graft survival in vivo, or decrease in proliferation/IL-2 production in vitro, was seen following prechallenge with B10.BR LPS blasts.
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PMID:Tolerance induction to multiple minor histoincompatible cells by activated B cells is associated with preferential activation of Th2 cells. 803 8

Acquired resistance to both Onchocerca volvulus and O. lienalis infective larvae, implanted within micropore chambers, could be induced in mice following immunization with irradiated L3 larvae. In experiments with O. volvulus in BALB/c and BALB/c. By mice, consistent levels of protection (61-75% reductions compared to challenge controls) were achieved with challenge infections of 2 week duration. In DBA/2 mice, levels of protection against O. lienalis were lower and more variable (42-63%): Moreover a 3 week period between challenge and recovery was required before significant reductions in larval recovery became detectable in vaccinated animals. Immunization of CBA or BALB/c mice with O. lienalis microfilariae, or CBA mice with normal or irradiated O. lienalis L3 larvae, failed to induce killing or growth retardation of developing larvae. Preliminary characterization of the effector mechanisms and cytokines associated with protective immunity against O. volvulus infective larvae revealed elevated levels of eosinophils in peripheral blood and within micropore chambers during challenge infections in vaccinated mice. Spleen cells from the same animals stimulated with parasite antigen induced significant levels of IL-5, IL-4 and IFN gamma. These cytokines were barely detectable in antigen stimulated cells from challenge control mice.
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PMID:Protective immunity against Onchocerca volvulus and O. lienalis infective larvae in mice. 806 76

The present study deals with the effect of transforming growth factor-beta (TGF-beta) on anti-tumor immune responsiveness at various stages of the tumor-bearing state. Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1-3 wk after inoculation with CSA1M cells produced interleukin-2 (IL-2) and macrophage-activating factor (MAF)/interferon-gamma (IFN-gamma) upon in vitro culture without addition of exogenous tumor antigens. This lymphokine production was achieved through collaboration between anti-CSA1M CD4+ T cells and antigen-presenting cells that had been pulsed with CSA1M tumor antigens in vivo in the tumor-bearing state. The IL-2-producing capacity of CD4+ T cells reached the maximal level as early as one week after tumor implantation but decreased with the progress of tumor-bearing stages. In contrast, the capacity of CD4+ T cells to produce MAF/IFN-gamma was not affected but was maintained at high levels even late in the tumor-bearing state. The addition of recombinant TGF-beta (rTGF-beta) to cultures of spleen cells from various tumor-bearing stages resulted in the suppression of lymphokine production. However, the magnitude of the TGF-beta-induced suppression varied depending on which tumor-bearing stages of splenic cells were tested as a responding cell population; it was slight in cells from early (1-3 wk) tumor-bearing stages but increased in cells from donor mice at later tumor-bearing stages. Thus, spleen cells from late tumor-bearing stages with weak but significant IL-2-producing and considerable MAF/IFN-gamma producing capacities failed to produce these lymphokines when rTGF-beta was present in cultures. A progressive increase in the TGF-beta susceptibility was also observed for IL-4-producing Th2 as well as IL-2/MAF-producing Th1 cells. In addition, increased levels of TGF-beta were detected in plasma from tumor-bearing mice at late stages. Taken together, these results indicate that tumor-bearing mice exhibit enhanced production of TGF-beta as well as a progressive increase in the susceptibility of anti-tumor CD4+ T cells to TGF-beta-induced suppressive mechanisms.
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PMID:Transforming growth factor-beta (TGF-beta)-mediated immunosuppression in the tumor-bearing state: enhanced production of TGF-beta and a progressive increase in TGF-beta susceptibility of anti-tumor CD4+ T cell function. 809 27


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