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)

We describe the adoptive transfer of erosive arthritis to an immunodeficient host. Spleen cells from arthritic DBA/1 mice (H-2q), immunized 4-6 weeks previously with bovine type II collagen in adjuvant, were transferred intraperitoneally into SCID mice (H-2d). SCID recipient mice also received native or denatured type II collagen (100 micrograms intraperitoneally) at the time of cell transfer. Arthritis developed in five out of five mice approximately 2 weeks after injection of cells plus native collagen, whereas animals injected with cells plus denatured collagen did not show any clinical or histological evidence of arthritis. The minimum graft size required for successful transfer of arthritis was established at 10(7) DBA/1 spleen cells. Histological examination of the joints of arthritic SCID recipient mice revealed synovitis, fibrosis and erosion of cartilage and underlying bone. Mean circulating levels of anti-type II collagen IgG were found to be significantly higher in mice injected with native collagen than those injected with denatured collagen (40 micrograms/ml and less than 1 microgram/ml, respectively). The ability to transfer collagen-induced arthritis adoptively should facilitate the study of the cellular requirement and pathological mechanisms involved in the induction of this arthropathy.
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PMID:Successful transfer of collagen-induced arthritis to severe combined immunodeficient (SCID) mice. 160 30

T-cell lines were established from the lymph node cells of syngeneic Louvain (LOU) rats previously immunized with native chick type II collagen (CII) emulsified in incomplete Freund's adjuvant. The CII lines proliferated in vitro to type II collagen but not to type I collagen, ovalbumin (OV), or PPD. Control lines, developed from LOU rats immunized with OV emulsified in complete Freund's adjuvant, were OV specific because they did not respond to other antigens in vitro. CII line cells could adoptively transfer delayed-type hypersensitivity (DTH) but did not induce IgG antibody production to collagen. Moreover, the intravenous administration of 2 X 10(7) CII line cells prevented the subsequent induction of collagen arthritis following immunization and suppressed DTH to collagen without affecting antibody responses in the recipients. Spleen cells, but not sera, from these resistant rats decreased CII line reactivity in vitro. OV or irradiated CII lines had no effect on clinical or immunologic parameters in this model. These findings demonstrate protection from arthritis afforded by T-cell line transfer and suggest that the phenomenon results from down-regulation of the recipients' cellular immunity to collagen.
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PMID:Attenuation of collagen arthritis and modulation of delayed-type hypersensitivity by type II collagen reactive T-cell lines. 349 39

Rats were immunized with type II collagen to induce polyarthritis. Spleen and lymph node cells were taken at various times and transferred to normal syngeneic animals. Disease was not observed in recipients of cells taken from donors either during the pre-clinical phase or the acute clinical phase of the disease. However, arthritis could not be induced in the recipient animals that had received cells taken from donors during the preclinical phase. Animals receiving cells from donors with clinical disease appeared to have a normal susceptibility to disease induced subsequently. In contrast with the differences in their susceptibility to induced disease, all recipient animals made unmodified antibody responses to a challenging injection of type II collagen. The results showed that before the appearance of clinical disease in CII immunized rats, there were cells in the spleen and lymph nodes that inhibit the development of disease but not antibody responses.
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PMID:Suppression of collagen type II-induced arthritis by transfer of lymphoid cells from rats immunized with collagen. 404 27

Dendritic cells, such as epidermal Langerhans cells, play a crucial role for the antigen-specific priming of T cells. We have addressed the question whether dendritic cells present collagen, a major protein component in tissues through which dendritic cells migrate, i.e. the basement membrane, dermis, and synovial tissue. Langerhans cells, spleen cells and peritoneal macrophages were compared for antigen-presenting capacity using a panel of mouse T cell hybridomas reactive with different determinants on type II collagen, myelin basic protein, ovalbumin and pepsin. Langerhans cells did not present any of the type II collagen determinants, unless the antigen was administered as a 15-mer peptide, but did present myelin basic protein, ovalbumin and pepsin. Spleen cells and peritoneal macrophages, in contrast, presented all type II collagen determinants. This biased antigen presentation was also observed when Langerhans cells were pulsed with antigen in vivo. The inability to present type II collagen is related to the collagen sequence as such, since both native type II collagen, type II collagen alpha chains, as well as a type II collagen determinant incorporated in type I collagen, were not presented by Langerhans cells. In addition, granulocyte/macrophage colony-stimulating factor-expanded blood dendritic cells displayed the same biased antigen presentation, suggesting that the inability to present collagen is not restricted to dendritic cells localized in epidermis. B cell-deficient mice could prime a type II collagen-reactive T cell response, thus excluding B cells as obligatory antigen-presenting cells for the priming of collagen-reactive T cells. We suggest that neither Langerhans cells nor B cells, but macrophages are the primary antigen-presenting cells in the immune response towards type II collagen.
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PMID:Macrophages, but not dendritic cells, present collagen to T cells. 754 14

The role of T lymphocytes in the adoptive transfer of collagen-induced arthritis (CIA) in DBA/1J mice to severe combined immunodeficient (SCID) mice was investigated. Spleen cells from non-immunized, type I collagen (CI) or type II collagen (CII)-immunized DBA/1J mice were injected into SCID mice which lack functional T and B cells. Specific antigenic stimulation of arthritogenic cells was required since only lymphocytes from arthritic CIA mice plus simultaneous administration of CII transferred arthritis to 11 of 12 SCID mice with a marked increase in CII antibody titre. However, CI-immunized or non-immunized DBA/1J mice cells did not induce arthritis in SCID mice. SCID recipients of pre-arthritic CIA lymphocytes presented increase in CII antibody, but showed no clinical signs of arthritis, suggesting that antibodies to CII alone can not induce CIA. Depletion of CD4+ T cells inhibited the transfer of arthritis to SCID mice, with a decrease in CII antibody titre in chimaeras. In contrast, depletion of CD8+ T cells enhanced the onset of arthritis in SCID mice. The results imply that CD4+ T cells are required for the induction of CIA. In addition, CD8+ T cells might have a suppressive role in the etiology of this disease. It is probable that memory CD4+ T cells stimulate production of antibodies to CII and subsequent arthritis. This study clarifies the role of T lymphocytes in the transfer of CIA to SCID mice.
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PMID:CD4+ T cells from collagen-induced arthritic mice are essential to transfer arthritis into severe combined immunodeficient mice. 791 55

We developed a convenient and reliable procedure for the cell-mediated passive transfer of type II collagen (CII)-induced arthritis (CA). Spleen cells from DBA/1 mice with CA were intravenously transferred into syngeneic recipient mice. Arthritis developed only in those recipients which had received whole-body x-irradiation (8 Gy) just before cell transfer and intraperitoneally given soluble CII without adjuvant immediately after transfer. Non-immunized splenocytes could not induce arthritis even in irradiated recipients given soluble CII. Development of arthritis depended on the number of cells transferred; 5 x 10(7) cells induced severe and long-lasting arthritis in every recipient approximately 10 days after transfer. Severity of this arthritis was clinically and histologically similar to classical CA in donors. Arthritogenic splenocytes were generated in donors no later than 20 days after priming with CII in Freund's complete adjuvant, when arthritis had yet to occur, and were detected for more than 5 weeks. One splenocyte population responsible for transferring arthritis was CD4+ T cells. We then applied this system to show that prophylactic treatment of CII-immunized mice with cyclophosphamide (CY, 7 mg/kg), but not interferon-gamma (IFN-gamma, 10(5) U/mouse), suppressed the arthritogenic ability of their spleen cells, although both treatments inhibited the development of CA. Treatment of recipients with IFN-gamma, however, inhibited the development of arthritis upon transfer with CII-immunized splenocytes. These results indicate that CY and IFN-gamma act at the induction and effector phases of arthritogenic lymphocytes, respectively. Thus, this system facilitates investigation of pathological mechanisms of CA, and of mechanisms of anti-arthritics.
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PMID:Cell-mediated transfer of collagen-induced arthritis in mice and its application to the analysis of the inhibitory effects of interferon-gamma and cyclophosphamide. 809 77

There is considerable interest in the possible use of cAMP-elevating agents in the treatment of autoimmune diseases such as rheumatoid arthritis. The objective of this study was to evaluate the impact of different cAMP-elevating agents on the T-cell response to type II collagen within the context of collagen-induced arthritis, a murine model of rheumatoid arthritis. Spleen cells or lymph node cells from type-II-collagen-immunized DBA/1 mice were cultured in the presence of type II collagen plus one of five different cAMP-elevating agents: rolipram, forskolin, prostaglandin E2, 8-bromo-cAMP, or cholera toxin. Levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-5 were measured in culture supernatants by enzyme-linked immunosorbent assay. All of the cAMP-elevating agents tested were found to profoundly suppress IFN-gamma production in a dose-dependent manner. IL-4 and IL-5 production was slightly up-regulated at low concentrations of the cAMP-elevating agents and was modestly suppressed at the highest concentrations of cAMP-elevating agents. Experiments were then carried out to determine whether T cells were directly affected by cAMP-elevating agents or whether the immunomodulatory effects were mediated via antigen-presenting cells. Pulsing T cells alone for a brief period with cholera toxin produced an almost identical effect to pulsing antigen-presenting cells alone, i.e. down-regulation of proliferation, down-regulation of IFN-gamma production with little effect on IL-5 production. It was concluded that cAMP-elevating agents suppressed T helper type 1 responses to type II collagen to a greater extent than T helper type 2 responses. The cAMP-elevating agents could directly influence the activity of T cells but, in addition, influenced the ability of antigen-presenting cells to support T helper type 1 responses.
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PMID:Impact of cAMP on the T-cell response to type II collagen. 1467 97