Accessory signaling by CD40 for T cell activation: induction of Th1 and Th2 cytokines and synergy with interleukin‐12 for interferon‐γ production

Peng, Xiaohui; Kasran, Ahmad; Warmerdam, Petra A. M.; Boer, Mark de; Ceuppens, Jan L.

doi:10.1002/eji.1830260732

Cited by 120 publications

(74 citation statements)

References 30 publications

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“…IL-4, IL-5 and IL-10 by human T cells is strongly Ž . enhanced by CD40L ligation Peng et al, 1996 . Importantly, in progressive MS, activated CD4 q T cells stimu-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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“…IL-4, IL-5 and IL-10 by human T cells is strongly Ž . enhanced by CD40L ligation Peng et al, 1996 . Importantly, in progressive MS, activated CD4 q T cells stimu-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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“…Tumor necrosis factor-␣ (TNF-␣) concentration in supernatants was determined with the Innotest hTNF-alpha kit (Innogenetics, Gent, Belgium). IL-2, IL-4, IL-5, IL-10 and interferon-␥ (IFN-␥) concentrations were determined with a sandwich ELISA technique, using combinations of unlabelled and biotin-coupled mAb to different epitopes of each cytokine as described 28 (anti-IL-2 mAb was obtained…”

Section: Cytokine Production and Detectionmentioning

confidence: 99%

CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

et al. 1998

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Three-color flow cytometry immunophenotyping revealed significant increases of CD57 + and CD28 − cells among both circulating CD4 + and CD8 + T lymphocytes of untreated hemato-oncological patients (n = 54) as compared to healthy donors (n = 55), with CD57 and CD28 expression on the patients' T cells being largely reciprocal. Marked expansion of CD57 + cells among circulating CD4 + T lymphocytes was frequently detected in patients with chronic leukemia of B cell origin (B-CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia, suggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation techniques, we further demonstrate that the patients' CD57 + /CD28 − T cells display a typical Th1-type cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher secretion of the Th1-type cytokines IL-2, IFN-␥, and TNF-␣ than their CD57 − /CD28 + counterparts. Cytotoxic activity of circulating CD8 + T lymphocytes, measured ex vivo in an anti-CD3-redirected assay, was almost exclusively exerted by the CD57 + /CD28 − subset. Moreover, a marked cytotoxic activity was detected within CD4 + CD57 + T cells from some B-CLL patients. Finally, the patients' CD57 + /CD28 − T cells displayed an increased tendency to apoptosis in culture. Collectively, our results indicate that the expanded CD57 + /CD28 − T cells in hemato-oncological patients represent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear.

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“…Tumour necrosis factor-alpha (TNF-a) concentration in supernatants was determined with the Innotest hTNF-alpha kit (Innogenetics, Gent, Belgium). IL-2, IL-4, IL-5, IL-10, and interferon-gamma (IFN-g) concentrations were determined with a sandwich ELISA technique, using combinations of unlabelled and biotin-coupled MoAbs to different epitopes of each cytokine, as described [19]. …”

Section: Cytokine Production and Detectionmentioning

confidence: 99%

Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma

Hove¹,

Gool²,

Poppel³

et al. 1997

Clinical and Experimental Immunology

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SUMMARYWe investigated the phenotype and functional capacities of tumour-infiltrating lymphocytes (TIL), freshly isolated from primary renal cell carcinoma (RCC) specimens (n ¼ 20). Three-colour flow cytometry immunophenotyping revealed that RCC TIL consist mainly of CD3 þ T cells, with a clear predominance of CD4 ¹ CD8 þ over CD4 þ CD8 ¹ T cells, and a marked population of CD4 þ CD8 þ T cells. Natural killer (NK) cells were also strongly represented (> 25% in 15 of 20 tumour samples), while B cells constituted a minor TIL subset (< 5% in 18 of 20 tumour samples). More importantly, the T and NK cells within the tumour displayed a significantly higher expression of the early activation marker CD69 than their counterparts in adjacent normal renal tissue and in peripheral blood. Expression of CD54 and of HLA-DR was also elevated on CD3 þ TIL, and HLA-DR expression was further vigorously up-regulated following ex vivo stimulation with anti-CD3, all suggesting enhanced immune activity within the tumour microenvironment. CD3 þ CD4 þ TIL displayed a normal capacity to up-regulate CD25 expression and to secrete both Th1-type (IL-2, tumour necrosis factor-alpha (TNF-a) and interferon-gamma (IFN-g)) and Th2-type (IL-4, IL-5 and IL-10) cytokines upon triggering with anti-CD3. Furthermore, cytokine production was susceptible to modulation by CD28 costimulation. CD3 þ CD8 þ TIL, on the other hand, consistently demonstrated a poor up-regulation of CD25 upon triggering with anti-CD3, and displayed poor ex vivo cytolytic activity in an anti-CD3-redirected 4-h cytotoxicity assay against murine P815 cells. Collectively, our findings indicate that the CD3 þ CD4 þ TIL in RCC have normal functional capacities, whereas the proportionally major CD3 þ CD8 þ TIL are functionally impaired. The relevance of these findings to the in vivo local immune response in RCC is discussed.

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Accessory signaling by CD40 for T cell activation: induction of Th1 and Th2 cytokines and synergy with interleukin‐12 for interferon‐γ production

Cited by 120 publications

References 30 publications

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

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

CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma

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