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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

Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1 M) 2 to 3 wk after inoculation with CSA1 M cells produced IL-2, IFN-gamma, and TNF upon in vitro cultures. This was previously demonstrated to be a result of collaboration between tumor-primed CD4+ T cells and APCs binding CSA1 M tumor Ags in vivo. The IL-2- and IFN-gamma-producing capacities decreased with the progress of tumor-bearing stages. This was parallel to the levels of IL-2 and IFN-gamma mRNAs expressed by cultured spleen cells. In contrast, comparable levels of TNF mRNA were expressed by all groups of cultured cells. However, large amounts of TNF were secreted by the cells from early but not from late tumor-bearing mice. TNF was produced mainly by the non-T cell fraction upon stimulation with CD4+ T cell-derived IFN-gamma. Therefore, the reduced TNF production by whole spleen cells from late tumor-bearing mice was restored by addition of rIFN-gamma to their cultures. Reciprocally to the progressive decrease in the production of IFN-gamma/TNF, the capacities of tumor-bearing mice to produce TGF-beta and IL-6 increased along with tumor growth. TGF-beta suppressed production of IL-2, IFN-gamma, and TNF, but not of IL-6. Moreover, IFN-gamma/TNF production was negatively regulated by IL-6. Taken together with the fact that the growth of CSA1 M cells is completely inhibited by the combination of TNF and IFN-gamma, these results demonstrate that the tumor-bearing state induces an abnormal cytokine network under which the production of antitumor cytokines is negatively regulated.
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PMID:Regulatory mechanisms for production of IFN-gamma and TNF by antitumor T cells or macrophages in the tumor-bearing state. 786

Although it is well known that cellular rejection is mediated by alloreactive lymphocytes, several investigators, including our group, have shown that such cells are a rather small proportion of the T cell infiltrate of the alolograft. We have therefore postulated that graft-infiltrating lymphocytes must recognize other antigens. Since heat shock protein (hsp)-specific lymphocytes have been shown to participate in several autoimmune diseases and in tumor immunity, we hypothesized that hsp-reactive lymphocytes are involved with allograft rejection. This hypothesis was tested with a rat model of heterotopic MHC-incompatible cardiac allografts (ACI into Lewis), whereby graft-infiltrating lymphocytes and spleen cells were tested in vitro with different recombinant mycobacterial hsp preparations. As expected, allograft lymphocytes showed proliferative responses to irradiated spleen cells from the donor. This proliferation was markedly augmented by hsp65 (3-fold) and hsp70 (5-fold), whereas hsp10 and the protein control ovalbumin had no effect. Proliferation of allograft lymphocytes to hsp in context with syngeneic splenocytes as antigen-presenting cells (APC) was seen primarily if small quantities of IL-2 had been added to the cultures. In contrast, hsp-specific proliferation was never observed with syngraft lymphocytes, even after addition of IL-2. Spleen cells from allograft and syngraft recipients showed hsp augmentation of alloproliferation, but the magnitude was less than that with allograft lymphocytes. Kinetic studies showed that hsp-reactive lymphocytes first appeared in the allograft on day 3 posttransplant. Tacrolimus immunosuppression of transplant rejection prevented the appearance of hsp-reactive lymphocytes in allografts. Culture conditions have been established to generate hsp65- and hsp70-specific T lymphocyte lines and clones from allograft-infiltrating cells. These cultured cells exhibited hsp reactivity only in context with self-APC, and this was augmented by small amounts of IL-2. These data provide strong evidence for the involvement of hsp-reactive lymphocytes in allograft rejection. We propose the concept that during rejection tissue stress induced by alloreactive effector lymphocytes promotes the recruitment and activation of hsp-reactive lymphocytes, especially in the presence of IL-2 released into the allogeneic environment of the transplant. These hsp-reactive T cells may play a role in the immune cascade of the inflammatory process of transplant rejection.
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PMID:Heat shock protein reactivity of lymphocytes isolated from heterotopic rat cardiac allografts. 787 64

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

Local IL-2 administration prior to transplantation of murine sarcoma virus (MSV Harvey)-induced tumour MSVT2 provided a model of slowly growing tumours suitable for long-term investigation of the therapeutic efficacy of repeated IL-2 injection cycles. Challenge of mice with the dose of sarcoma cells, which was lethal for 20/20 untreated control recipients, revealed that 8/20 IL-2-pretreated mice were protected by the local IL-2 treatment and survival indefinitely. Nine out of twenty IL-2-pretreated mice died during the same time period as the control mice, i.e., during 36 days, and 3/20 IL-2 pretreated mice were tumour-negative until day 60, when incipient tumours arose. The three late tumours were used as a model to investigate the therapeutic efficacy of the new cycles of repeated local IL-2 administration. It was found that no resistance to IL-2 immunotherapy was induced by pretreatment of the late tumours and that the tumours were repeatedly susceptible to local IL-2 treatment. Spleen cells of the tumour-bearing mice, which were not cytotoxic for MSVT2 tumour cells in vitro, could be made cytotoxic by addition of exogenous IL-2.
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PMID:Therapeutic efficacy of repeated cycles of local IL-2 injections in mice carrying slowly growing tumour grafts. 792 62

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

We have generated transgenic mice expressing the human (h) IL-2R beta-chain on lymphoid cells under the control of the mouse H-2Kd promoter. Spleen cells and thymocytes of the transgenic mice were cultured in the presence of 5 nM hIL-2. After a 10-day culture, the expanded populations were analyzed by flow cytometry and shown to be composed of CD8+ T cells and gamma delta T cells. Surprisingly, CD4+ T cells of the transgenic mice did not proliferate in response to hIL-2, although the CD4+ T cells expressed the transgenic hIL-2R beta-chain as well as the endogenous gamma-chain on their surface and bound 125I-labeled IL-2. When CD4+ T cells of the transgenic mice were stimulated with anti-CD3 mAb, the CD4+ T cells proliferated in response to hIL-2. These findings suggest that CD4+ T cells may require another triggering signal to respond to IL-2 even when IL-2Rs are expressed. By contrast, CD8+ T cells and gamma delta T cells respond to IL-2 as long as IL-2Rs are expressed.
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PMID:IL-2 can support growth of CD8+ T cells but not CD4+ T cells of human IL-2 receptor beta-chain transgenic mice. 798 43

Spleen and lymph node cells of Trypanosoma cruzi-infected mice were studied for mitogen-induced responsiveness in terms of proliferation and lymphokine production (IL-2, IFN-gamma). Splenocyte (SP) as well as lymph node cell (LN) proliferation and IL-2 production were depressed during the acute phase of the infection. Proliferative capacity of LN cells recovered completely and that of SP partially during the chronic phase. In contrast to these suppressive effects, the mitogen-induced IFN-gamma response was enhanced. In vitro co-incubation of normal SP or LN cells with trypomastigotes resulted in a reduced mitogen-induced cell proliferation and IL-2 secretion, similar to those seen with cells taken from infected mice. In contrast, trypomastigotes exerted a stimulatory activity on the mitogen-induced IFN-gamma response of both SP and LN cells. Addition of lymph node cells from T. cruzi-infected mice (LN-I) to lymph node cells of control mice (LN-C) suppressed strongly the mitogen-induced responsiveness of such cocultures. A marginal level of suppression was recorded in cocultures of spleen cells from infected mice (SP-I) and control spleen cells (SP-C). The potent suppressive cells within LN-I populations were identified as macrophage-like and such cells were absent in SP-C and peritoneal exudate cells from T. cruzi infected animals.
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PMID:Modulation of T-cell responsiveness during Trypanosoma cruzi infection: analysis in different lymphoid compartments. 801 58

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

C57BL/6Kh mice were infected with a single i.p. injection of 1 x 10(5) FFU of LP-BM5 MuLV. The development and progress of the virus-induced lymphoproliferative disease was followed for 12 weeks after infection. As anticipated, progressive splenomegaly and lymphadenopathy, as well as almost total abrogation of immune responsiveness ensued. In contrast to previous reports, there was a dramatic increase in the frequency of CD4+ cells in spleens among which over 20% expressed V beta 5 TCR, as compared with fewer than 3% in spleens of normal mice. Spleen cells from infected mice retained their in vitro ability to proliferate upon stimulation with IL-2 and anti-CD3, but were unable to respond when stimulated with phorbol ester and either a low dose of IL-2 or calcium ionophore (ionomycin). A similar pattern of in vitro proliferative responses was obtained when normal spleen cells were treated with K252a compound, a known inhibitor of protein kinase C activity. Together with the observations that viral infection impaired down-regulation of the phorbol-induced kinase activity and that the kinase inhibitor only marginally enhanced suppression of virus-infected cells proliferation, this finding suggests that disturbances of protein kinase C activity may underly the pathological effects seen after viral infection. However, since no apparent quantitative and qualitative changes in protein kinase C itself and its translocation were observed, it is more likely that the virus may interfere with either the substrate or product of kinase activity.
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PMID:Acquired immunodeficiency in murine lymphoproliferative disease: considerations on pathogenesis. 808 52


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