Chagasic Patients with Indeterminate Clinical Form of the Disease have High Frequencies of Circulating CD3+CD16–CD56+ Natural Killer T Cells and CD4+CD25High Regulatory T Lymphocytes

Vitelli-Avelar, Danielle Marquete; Sathler-Avelar, Renato; Dias, João Carlos Pinto; Pascoal, Vanessa Peruhype Magalhães; Teixeira-Carvalho, A.; Lage, Paula S.; Elói-Santos, Silvana Maria; Corrêa-Oliveira, Rodrigo; Martins‐Filho, Olindo Assis

doi:10.1111/j.1365-3083.2005.01668.x

Cited by 89 publications

(80 citation statements)

References 51 publications

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“…Others have shown a direct effect of Treg on antigen-presenting cells (24,25). Recently, an effect of Treg on NK cells was demonstrated (26); however, we showed recently that NK cells are not important in the murine AN (27), so it is unlikely that such an interaction explains the protective effect of CD4 ϩ CD25 ϩ Treg in our study.…”

Section: Discussioncontrasting

confidence: 52%

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

Mahajan

Wang

Qin

et al. 2006

Journal of the American Society of Nephrology

127

106

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Studies of mechanisms of disease regulation by CD4؉ CD25 ؉ regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4 ؉ CD25 ؉ Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4 ؉ CD25 ؉ T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4 ؉ CD25 ؉ T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF-␤ using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF-␤-dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.

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Section: Discussioncontrasting

confidence: 52%

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

Mahajan

Wang

Qin

et al. 2006

Journal of the American Society of Nephrology

127

106

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“…On the other hand, the cytokines IL-10 and transforming growth factor ␤ (TGF-␤) counterregulate the inflammatory process, indirectly favoring parasite persistence within infected host cells because they are potent inhibitors of nitric oxide (NO) production and other IFN-␥-and IL-12-mediated cell activation processes that are important for the killing of the parasite (12,32). The extent of this regulation seems to be crucial for the final outcome of the illness, since patients with the indeterminate (asymptomatic) form of the disease have a more controlled immune response (38) than patients with advanced stages of infection.…”

Section: Trypanosoma Cruzi Infection Causes Intense Myocarditis Leadmentioning

confidence: 99%

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor 1

et al. 2011

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Trypanosoma cruzi infection causes intense myocarditis, leading to cardiomyopathy and severe cardiac dysfunction. Protective adaptive immunity depends on balanced signaling through a T cell receptor and coreceptors expressed on the T cell surface. Such coreceptors can trigger stimulatory or inhibitory signals after binding to their ligands in antigen-presenting cells (APC). T. cruzi modulates the expression of coreceptors in lymphocytes after infection. Deregulated inflammation may be due to unbalanced expression of these molecules. Programmed death cell receptor 1 (PD-1) is a negative T cell coreceptor that has been associated with T cell anergy or exhaustion and persistent intracellular infections. We aimed to study the role of PD-1 during T. cruzi-induced acute myocarditis in mice. Cytometry assays showed that PD-1 and its ligands are strongly upregulated in lymphocytes and APC in response to T. cruzi infection in vivo and in vitro. Lymphocytes infiltrating the myocardium exhibited high levels of expression of these molecules. An increased cardiac inflammatory response was found in mice treated with blocking antibodies against PD-1, PD-L1, and to a lesser extent, PD-L2, compared to that found in mice treated with rat IgG. Similar results in PD-1 ؊/؊ mice were obtained. Moreover, the PD-1 blockade/deficiency led to reduced parasitemia and tissue parasitism but increased mortality. These results suggest the participation of a PD-1 signaling pathway in the control of acute myocarditis induced by T. cruzi and provide additional insight into the regulatory mechanisms in the pathogenesis of Chagas' disease.Chagas' disease is the most important cause of acquired cardiomyopathy in Latin America and is one of the outcomes resulting from the interaction between the human immune system and the hemoflagellate prokaryote Trypanosoma cruzi. In the natural infection, the flagellated forms in the feces of infected hematophagous insects of the Triatominae subfamily invade the host through skin lesions or intact mucosa. The parasite then proliferates intracellularly and disseminates systemically from the site of inoculation, causing an inflammatory reaction of variable intensity, along with splenomegaly, cardiac parasitism, and myocarditis, which is largely associated with morbidity. More frequently, a chronic asymptomatic infection is established, which eventually leads to dilated cardiomyopathy and heart failure as well as esophageal or intestinal dilatations due to the combined effects of parasite persistence, immune deregulation, autonomic denervation, and microvascular damages (21,30).The immunological mechanisms underlying this silent, relentless infection and heart pathology remain elusive despite several decades of research. It is known that T cell-mediated immune responses are essential to control the parasite replication during the acute phase of the infection (33). The cytokines gamma interferon (IFN-␥), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-␣) strengthen the activation of innate and adaptive ...

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“…À/þ CD56 À/þ as described previously [Vitelli-Avelar et al, 2005]. Analysis of CD56 Dim and CD56 Bright cells was performed within CD3…”

Section: Flow Cytometric Analysis Of Peripheral Bloodmentioning

confidence: 99%

Increased frequency of CD56^Bright NK‐cells, CD3⁻CD16⁺CD56⁻ NK‐cells and activated CD4⁺T‐cells or B‐cells in parallel with CD4⁺CDC25^High T‐cells control potentially viremia in blood donors with HCV

Zarife

Reis

Carmo

et al. 2008

Journal of Medical Virology

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A detailed phenotypic analysis of major and minor circulating lymphocyte subsets is described in potential blood donors with markers of hepatitis C virus (HCV), including non-viremic and viremic groups. Although there were no changes in the hematological profile of either group, increased the levels of pre-NK cells (CD3 CD25High T-cells were significantly elevated in both the viremic and nonviremic groups, it was particularly evident in the viremic low viral load subgroup. A parallel increase in CD4 þ CD25 High T-cells, pre-NK, and activated CD4 þ T-cells was observed in the nonviremic group, whereas a parallel increase in CD4 þ CD25 High T-cells and CD19 þ B-cells was characteristic of the low viral load subgroup. These findings suggest that CD56Bright NK cells, together with pre-NK cells and activated CD4

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Chagasic Patients with Indeterminate Clinical Form of the Disease have High Frequencies of Circulating CD3⁺CD16^–CD56⁺ Natural Killer T Cells and CD4⁺CD25^High Regulatory T Lymphocytes

Cited by 89 publications

References 51 publications

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor 1

Increased frequency of CD56^Bright NK‐cells, CD3⁻CD16⁺CD56⁻ NK‐cells and activated CD4⁺T‐cells or B‐cells in parallel with CD4⁺CDC25^High T‐cells control potentially viremia in blood donors with HCV

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Chagasic Patients with Indeterminate Clinical Form of the Disease have High Frequencies of Circulating CD3+CD16–CD56+ Natural Killer T Cells and CD4+CD25High Regulatory T Lymphocytes

Cited by 89 publications

References 51 publications

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor 1

Increased frequency of CD56Bright NK‐cells, CD3−CD16+CD56− NK‐cells and activated CD4+T‐cells or B‐cells in parallel with CD4+CDC25High T‐cells control potentially viremia in blood donors with HCV

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Chagasic Patients with Indeterminate Clinical Form of the Disease have High Frequencies of Circulating CD3⁺CD16^–CD56⁺ Natural Killer T Cells and CD4⁺CD25^High Regulatory T Lymphocytes

Increased frequency of CD56^Bright NK‐cells, CD3⁻CD16⁺CD56⁻ NK‐cells and activated CD4⁺T‐cells or B‐cells in parallel with CD4⁺CDC25^High T‐cells control potentially viremia in blood donors with HCV