Th1- and Th2-cell commitment during infectious disease: asymmetry in divergent pathways

Janković, Dragana; Liu, Zhugong; Gause, William C.

doi:10.1016/s1471-4906(01)01975-5

Cited by 249 publications

(180 citation statements)

References 88 publications

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“…53 Based on the microarray gene-expression profiles and the cluster analysis, we found that injection of Al(OH) 3 resulted in an immunological profile which was more closely related to that of naïve mice than to that of DDA/MPL-injected mice. That Th2 responses are induced under more 'immunologically silent' conditions compared with Th1 responses is consistent with a default Th2 pathway, as suggested several years ago by Jankovic et al, 54 which states that during infectious disease a Th2 response will develop in the absence of Th1-promoting factors. More recently, the same group has found that parasite-induced Th2 responses are related to a dampening of Th1-stimulating immune reactions and a lack of MyD88-signalling.…”

Section: Discussionsupporting

confidence: 74%

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

et al. 2009

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T-helper 1 and T-helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection Introduction With the vast amount of information on T-cell differentiation that has been obtained in recent years, and in particular that on the role of pathogen-associated molecular patterns (PAMPs) in the induction of immune responses, it should in theory be possible to tailor vaccines and adjuvants to selectively induce cell-mediated/humoral and T-helper 1/T-helper 2 (Th1/Th2) responses. This would obviously have tremendous impact on the ongoing

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Section: Discussionsupporting

confidence: 74%

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

et al. 2009

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“…In fact, it has been described that a resistant murine strain to T. cruzi infection have lymphocytes producing IFN-+ , while lymphocytes from susceptible murine strain have an enhanced IL-4 production [24]. In the context of our current findings, we propose that cruzipain would play a key role during T. cruzi infection leading to a T2 type cytokine profile favoring the permanence of the parasite in the host [25].…”

Section: Discussionsupporting

confidence: 56%

Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite

Giordanengo¹,

Guiñazú²,

Stempin³

et al. 2002

Eur. J. Immunol.

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We recently demonstrated that humoral immune response to cruzipain, a major antigen of Trypanosoma cruzi parasite, is implicated in the pathogenesis of experimental Chagas' disease. In the present study, the spleen cell phenotype and the cytokine profile induced by cruzipain in immunized mice were analyzed. The results showed that cruzipain increases the number of spleen cells with large size and granularity. Splenocyte populations with CD19 + , Mac-1 + , Gr-1 + and CD11c + positive surface markers significantly increased in immune mice compared to controls ones. Histological study revealed the presence of high number of megacariocyte and granulocyte-macrophage progenitors, indicating extramedullary hemopoiesis in spleens of immune mice. The finding of high levels of IL-4, IL5 and IL-10 and low levels of IFN-+ and IL-12 in supernatants of immune cells stimulated with cruzipain indicates a preferential activation of T2 type cells in immune animals. To investigate the role of innate immunity cells, the classical and alternative metabolic pathways of spleen macrophages from immune mice stimulated by cruzipain were also studied. The results showed an increase of urea associated with a decrease of nitrite levels, suggesting that cruzipain upregulates the arginase way. Therefore, cruzipain leads to T2 type cytokine profile which may enhance the arginase via in the macrophages promoting a susceptible mechanism to infection. Thus, we postulate that during T. cruzi infection, cruzipain could be used by the parasite to spread inside the host.

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“…9 It has been suggested that antigen-presenting cells (APCs) play a crucial role in the skewing of Th1 and Th2 differentiation. 10,11 IL-12 is a heterodimeric cytokine composed of p40 and p35 which strongly promotes the differentiation of naive CD4 ϩ T cells to the Th1 phenotype and suppresses the synthesis of Th2-type cytokines. 12 IL-12 is produced primarily by APCs and the production is regulated by IL-10 and IFN-␥.…”

mentioning

confidence: 99%

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

Hino

Kweon

Fujihashi

et al. 2004

The American Journal of Pathology

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IL-12 consists of two disulfide-linked subunits, p40 and p35, that form functionally active heterodimers for the induction of Th1 cells. In contrast to IL-12 heterodimers, p40 monomers and homodimers possess inhibitory effects on Th1 cells leading to the creation of a Th2 environment. Although it has been shown that IL-12p40 acts as antagonist of IL-12p70 in vitro, no evidence is currently available whether IL-12p40 is functional in vivo. We now report that IL12p40 plays an important pathological role in an intestinal allergic disease. A high expression of IL12p40 protein was demonstrated in epithelial cells, dendritic cells, and macrophages in large but not small intestine of allergic diarrhea-induced mice. Interestingly, neutralization with anti-IL-12p40 mAbs reduced the incidence and delayed the onset of disease development. Lower levels of ovalbumin (OVA)-specific IgE Abs in serum were detected in anti-IL12p40 mAb-treated mice than in control Ab-treated mice. The secretion of Th2 cytokines and eotaxin by the mononuclear cells isolated from the large intestine of anti-IL-12p40 mAb-treated mice was significantly decreased. Finally, the removal of the IL-12p40 gene resulted in complete inhibition of disease development. These results show that over-expression of IL-12p40 is an important contributing factor for the generation of the dominant Th2-type environment in the large intestine of mice with allergic diarrhea.

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Th1- and Th2-cell commitment during infectious disease: asymmetry in divergent pathways

Cited by 249 publications

References 88 publications

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection

Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite

Pathological Role of Large Intestinal IL-12p40 for the Induction of Th2-Type Allergic Diarrhea

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