hematopoietic system
• deletion of HA-specific Valpha8.3+CD4+CD8- thymocytes indicates deletion of autoreactive CD4+ T cells, although a subset of clonotypic CD4+ T cells evades deletion and accumulates in spleens and lymph nodes
• modest increase in the percentages of CD4+CD8- Foxp3+ thymocytes and of CD4+Foxp3+ splenocytes, however, the numbers of these cells that express the clonotypic TS1(SW) TCR are reduced, reflecting severe deletion of clonotype-expressing thymocytes
• however, no differences between males and females is seen in the percentages of CD4+ T cells, of CD4+CD25+Foxp3+ cells, of CD4+IL-17+ cells, or of B cells in the joint-draining lymph nodesincrease in frequency of IL-17-secreting CD4+ T cells in the joint-draining lymph nodes and spleens of arthritic mice
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells exhibit reduced spleen and joint-draining lymph node cellularities and increased percentages of CD4+ T cells
• treatment with an anti-CD20 mAb results in lower frequencies of clonotypic cytokine-producing T cells in mice that do not develop arthritis
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• arthritic mice exhibit a higher level of serum IgG than control Tg(Tcra/Tcrb)#/0 mice
• serum IgG titers are highest in arthritic females and are lower in both arthritic and nonarthritic males
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells show reduced levels of serum IgG
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• CD4+ T cells undergo little or no proliferation response to APCs from these mice
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homeostasis/metabolism
• proinflammatory cytokine levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
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• interleukin-17 levels are higher in the serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
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• interleukin-6 levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
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immune system
N |
• perivascular infiltrates are not seen in the lungs of arthritic mice and no inflammation in the hearts and kidneys
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• deletion of HA-specific Valpha8.3+CD4+CD8- thymocytes indicates deletion of autoreactive CD4+ T cells, although a subset of clonotypic CD4+ T cells evades deletion and accumulates in spleens and lymph nodes
• modest increase in the percentages of CD4+CD8- Foxp3+ thymocytes and of CD4+Foxp3+ splenocytes, however, the numbers of these cells that express the clonotypic TS1(SW) TCR are reduced, reflecting severe deletion of clonotype-expressing thymocytes
• however, no differences between males and females is seen in the percentages of CD4+ T cells, of CD4+CD25+Foxp3+ cells, of CD4+IL-17+ cells, or of B cells in the joint-draining lymph nodesincrease in frequency of IL-17-secreting CD4+ T cells in the joint-draining lymph nodes and spleens of arthritic mice
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells exhibit reduced spleen and joint-draining lymph node cellularities and increased percentages of CD4+ T cells
• treatment with an anti-CD20 mAb results in lower frequencies of clonotypic cytokine-producing T cells in mice that do not develop arthritis
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• arthritic mice exhibit a higher level of serum IgG than control Tg(Tcra/Tcrb)#/0 mice
• serum IgG titers are highest in arthritic females and are lower in both arthritic and nonarthritic males
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells show reduced levels of serum IgG
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• CD4+ T cells undergo little or no proliferation response to APCs from these mice
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• proinflammatory cytokine levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
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• interleukin-17 levels are higher in the serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
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• interleukin-6 levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
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• joint-draining lymph nodes of arthritic females are larger than either arthritic or nonarthritic males
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• swollen joints show a high degree of synovitis
• males show lower synovitis and articular degeneration than females
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• adult mice develop overt joint swelling affecting both front and hind paws
• males exhibit a lower penetrance of arthritis, a delay in disease onset, and decreased severity of arthritis relative to females
• mice that do not show overt joint swelling do not exhibit synovitis or articular degeneration
• inflammatory arthritis develops in mice despite substantial deletion of autoreactive CD4+ T cells and despite the formation of Foxp3+ Tregs
• treatment with an anti-IL-17R mAb abrogates arthritis development in females
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells prevents arthritis development in the majority of mice
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skeleton
• swollen joints show a high degree of synovitis
• males show lower synovitis and articular degeneration than females
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• adult mice develop overt joint swelling affecting both front and hind paws
• males exhibit a lower penetrance of arthritis, a delay in disease onset, and decreased severity of arthritis relative to females
• mice that do not show overt joint swelling do not exhibit synovitis or articular degeneration
• inflammatory arthritis develops in mice despite substantial deletion of autoreactive CD4+ T cells and despite the formation of Foxp3+ Tregs
• treatment with an anti-IL-17R mAb abrogates arthritis development in females
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells prevents arthritis development in the majority of mice
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• swollen joints show a high degree of articular degeneration
• males show lower synovitis and articular degeneration than females
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