Mice deficient for the CD40 ligand

Xu, Jinbao; Foy, Teresa M.; Laman, Jon D.; Elliott, Eileen A.; Dunn, Jonathan J.; Waldschmidt, Thomas J.; Elsemore, Jennifer; Noelle, Randolph J.; Flavell, Richard A.

doi:10.1016/1074-7613(94)90073-6

Cited by 704 publications

(518 citation statements)

References 17 publications

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“…However, renal defects have not been described in patients with X-linked hyper-IgM syndrome (35). Similarly, renal abnormalities have not been reported in CD40L (36) or CD40 (37) knockout mice. Taken together, these data suggest that if CD40 plays a role in normal renal function, this effect is minor and/or can be replaced by other signals.…”

Section: Discussionmentioning

confidence: 89%

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

Yellin

D’Agati

Parkinson

et al. 1997

Arthritis & Rheumatism

147

115

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Objective. To investigate potential mechanisms by which CD40L-mediated signals may be involved in the pathogenesis of lupus glomerulonephritis (GN).Methods. Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens. Immunohistochemical studies were performed on frozen sections utilizing anti-CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we analyzed normal kidney specimens and specimens obtained from patients with IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease, idiopathic membranous GN, and antineutrophil cytoplasmic antibodypositive pauci-immune GN. Staining distribution was noted and staining intensity scored on a semiquantitative scale of 0 (no staining) to 3+ (intense staining).Results. In normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells, endothelial cells, and distal tubules but not proximal tubules. Glomerular and tubular CD40 expression was markedly up-regulated in class I11 and class IV lupus GN, where there was intense staining of crescents, proximal and distal tubules, and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus GN was similar to that in normal kidney. Interstitial mononuclear cells expressing CD40L were present in class IV lupus GN. However, these findings were not unique to lupus GN: up-regulation of CD40 and CD40L expres- Submitted for publication June 3, 1996; accepted in revised form July 17, 1996. sion was similarly observed in other inflammatory renal diseases.Conclusion. This study shows that CD40 is expressed on a variety of renal parenchymal and nonparenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class I11 and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.

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Section: Discussionmentioning

confidence: 89%

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

Yellin

D’Agati

Parkinson

et al. 1997

Arthritis & Rheumatism

147

115

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“…It is known that interaction between CD40L and CD40 plays a crucial role in T cell priming, and either CD40 deficiency or CD40L deficiency abrogates efficient IgG antibody production against T-dependent antigens (29)(30)(31). It is also known that OX40 ligation with OX40L activates naive T cells to produce Th2 cytokines and differentiate into Th2 cells (32,33) and promotes B cell production of antibodies to T-dependent antigens (34).…”

Section: Resultsmentioning

confidence: 99%

Suppression of autoimmune arthritis in interleukin‐1‐deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells

Saijo

Asano

Horai

et al. 2002

Arthritis & Rheumatism

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“…The interaction between CD40 and its ligand CD40L is required for T cell-dependent B cell activation and antibody production [10,15]. Mice deficient in CD40L or CD40 are unable to mount primary or secondary antibody response to T cell-dependent antigens, do not form germinal centers and display blockage of the Ig isotype switching [16,17]. Excessive BAFF expression and CD40-CD40L signaling have been linked to initiation and progression of many autoimmune diseases, including SLE, rheumatoid arthritis (RA) and SS [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjögren's syndrome

et al. 2008

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CD40L and B lymphocyte‐activating factor (BAFF), members of the TNF superfamily, play critical roles in B cell survival and activation, and in the regulation of humoral immunity. We previously reported that the adaptor molecule Act1 functions as a negative regulator of CD40‐ and BAFF‐mediated B cell survival. Here we demonstrated that mice deficient in Act1 developed systemic autoimmune disease with histological and serological features of human Sjögren's syndrome (SS), in association with systemic lupus erythematosus‐like nephritis. Analyses of Act1−/−CD40−/− and Act1−/−BAFF−/− double‐deficient mice revealed that Act1 regulates different stages of the disease development through its impact on both CD40‐ and BAFF‐mediated pathways. We found that Act1 modulates the survival of autoreactive B cells mainly through its negative regulatory role in BAFF‐mediated cell survival, while the effect of Act1 on autoantibody production is likely through modulation of CD40‐mediated T cell‐dependent antibody response. The impact of Act1 on both BAFF and CD40 pathways establishes Act1‐deficient mice as a unique model to study distinct steps of autoimmunity and regulation of self tolerance.

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Mice deficient for the CD40 ligand

Cited by 704 publications

References 17 publications

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

Suppression of autoimmune arthritis in interleukin‐1‐deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells

Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjögren's syndrome

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