Activated T cells induce interleukin‐12 production by monocytes via CD40‐CD40 ligand interaction

Shu, Uno; Kiniwa, Mamoru; Wu, Cheng-Hung; Maliszewski, Charles R.; Vezzio, Nadia; Hakimi, J; Gately, Maurice K.; Delespesse, Guy

doi:10.1002/eji.1830250442

Cited by 394 publications

(237 citation statements)

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“…This may be interpreted as a mechanism that controls CD40-CD40L interaction in a negative fashion. The application of a dimeric CD40 fusion protein strongly suppressed IL-12 production of monocytes in vitro [49]. Supposing that sCD40 has similar effects on CD40-CD40L interaction in vivo, it might profoundly influence the immune system.…”

Section: Discussionmentioning

confidence: 97%

“…Soluble CD40 has been demonstrated in vitro in the supernatants of B cell lines and bound to CD40L, which was thought to regulate CD40-CD40L interaction in a negative fashion [47,48]. A dimeric CD40 fusion protein effectively suppressed IL-12 production by monocytes in vitro [49]. Thus, sCD40 is a candidate molecule to explain the development of immunological disturbances seen in end-stage renal failure.…”

Section: Introductionmentioning

confidence: 99%

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Soluble CD40 in the serum of healthy donors, patients with chronic renal failure, haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) patients

Schwabe

Engelmann

Hess

et al. 1999

Clinical and Experimental Immunology

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SUMMARYCD40 and its ligand CD40L are key players in T cell-B cell interaction and T cell-antigen-presenting cell (APC) interaction. Inhibition of CD40-CD40L interaction leads to severe humoral and cellular immunodeficiency. In this study we examined the presence of soluble CD40 (sCD40) in the serum of haemodialysis (HD) patients, CAPD patients, chronic renal failure (CRF) patients and healthy donors in order to evaluate the possible involvement of CD40 in uraemic immunodeficiency. Soluble CD40 was detected in the serum of healthy donors (n ¼ 41) with a mean of 0·14 Ϯ 0·12 ng/ml and in the urine of healthy donors with a mean of 1·80 Ϯ 0·74 ng/ml. Soluble CD40 was highly elevated in all patients with impaired renal function. HD patients (n ¼ 22) had up to 100-fold elevated sCD40 levels with a mean concentration of 8·32 Ϯ 4·11 ng/ml, whereas CAPD patients (n ¼ 10) had considerably lower levels of sCD40 with a mean of 3·58 Ϯ 2·40 ng/ml. A strong correlation between sCD40 and serum creatinine levels was noted in CRF patients (n ¼ 66). The highly elevated levels of sCD40 may point to the involvement of CD40 and its ligand CD40L in the clinical manifestation of uraemic immunodeficiency.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Soluble CD40 in the serum of healthy donors, patients with chronic renal failure, haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) patients

Schwabe

Engelmann

Hess

et al. 1999

Clinical and Experimental Immunology

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“…tion function of macrophages Kiener et al, 1995 . Functionally, CD40L supplied a costimulus for production of the pro-inflammatory cytokines TNF-a, IL-1b, IL-6, IL-8 Ž and IL-12 Alderson et al, 1993;Wagner et al, 1994;Shu et al, 1995;Kennedy et al, 1996 . Ž .…”

Section: Accessory Molecules: Cd40-cd40lmentioning

confidence: 99%

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Laman

Meurs²,

Schellekens³

et al. 1998

Journal of Neuroimmunology

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Ž .Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis MS and experimental autoimmune Ž . encephalomyelitis EAE in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of Ž . marmoset monkeys Callithrix jacchus with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions Ž . Ž . may result from local CD40-CD40L interactions. CD40 ligand CD40L and B7-2 CD86 were also expressed, but to a lower extent, Ž . while B7-1 CD80 expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual Ž . lesions during active disease IFN-a, IFN-g , TNF-a, IL-1a , IL-1b, IL-2, IL-4, IL-10 and IL-12 . This suggests that relative levels rather than sequential expression of Th1-and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention. q

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“…The best-defined costimulatory pathways are the B7:CD28 pathway and the CD40:CD40 ligand (CD40L) 4 pathway (1, 2). The two known members of the B7 family, B7-1 (CD80) and B7-2 (CD86), are expressed on professional APCs, and their expression is enhanced by microbes and innate immune responses.…”

mentioning

confidence: 99%

“…The interaction between CD40L and CD40 also enhances T cell responses (2,3). Although the mechanism of this effect is unclear, it is currently believed that CD40:CD40L interactions serve to up-regulate the expression of B7 on APCs and to induce the production of cytokines, such as IL-12, which promote T cell differentiation (4).…”

mentioning

confidence: 99%

The Roles of CD28 and CD40 Ligand in T Cell Activation and Tolerance

Howland

Ausubel

London

et al. 2000

The Journal of Immunology

160

105

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Costimulation of T cell activation involves both the B7:CD28 as well as the CD40 ligand (CD40L):CD40 pathway. To determine the importance of these pathways to in vitro and in vivo T cell activation, a direct comparison was made of the responses of TCR transgenic T cells lacking either CD28 or CD40L. In vitro, CD28−/− T cells showed a greater reduction in proliferative responses to Ag than did CD40L−/− T cells. The absence of CD28 resulted in defective Th2 responses, whereas CD40L−/− T cells were defective in Th1 development. In vivo, CD28−/− T cells failed to expand upon immunization, whereas CD40L−/− T cells could not sustain a response. These results suggest that CD28 is critical for initiating T cell responses, whereas CD40L is required for sustained Th1 responses. The different functional roles of these costimulatory pathways may explain why blocking B7:CD28 and CD40L:CD40 interactions has an additive effect in inhibiting T cell responses.

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Activated T cells induce interleukin‐12 production by monocytes via CD40‐CD40 ligand interaction

Cited by 394 publications

References 21 publications

Soluble CD40 in the serum of healthy donors, patients with chronic renal failure, haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) patients

Soluble CD40 in the serum of healthy donors, patients with chronic renal failure, haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) patients

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

The Roles of CD28 and CD40 Ligand in T Cell Activation and Tolerance

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