The effect of TGF-β1 on immune responses of naïve versus memory CD4+ Th1/Th2 T cells

Lúðvíksson, Björn Rúnar; Seegers, Diana; Resnick, Andrew S.; Strober, Warren

doi:10.1002/1521-4141(200007)30:7<2101::aid-immu2101>3.3.co;2-g

Cited by 41 publications

(46 citation statements)

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“…This indicates that the type 1 response is opposed by TGF‐β rather than by a type 2 response during L. chagasi infection. The low levels of IL‐4 in IL‐12KO and in BALB/c mice in our prior studies 6, 7 are consistent with the fact that TGF‐β is able to suppress both type 1 and type 2 CD4 + cell development 14, 15, 29. Thus the propensity of L. chagasi to induce a type 3 immune response dominates over the type 2 response in IL‐12KO mice 20.…”

Section: Discussionsupporting

confidence: 81%

“…Cytokines that inhibit type 1 responses include the type 2 cytokines (IL‐4, IL‐10, IL‐13), and the inhibitory cytokine TGF‐β 14. TGF‐β can inhibit both Th1 and Th2 cell development, and it has been shown to suppress cytokine production by type 1 but not type 2 memory cells 15. It is not known whether the propensity to elicit TGF‐β rather than a type 2 response is due to characteristics of the infecting species of Leishmania , or whether this is a unique response of BALB/c mice to L. chagasi infection.…”

Section: Introductionmentioning

confidence: 99%

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The TGF-? response toLeishmania chagasi in the absence of IL-12

et al. 2002

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Cure of leishmaniasis requires a type 1 immune response characterized by IFN‐γ production. Leishmania major infection leads to a type 2 response suppressing cure of susceptible BALB/c mice, and L. major causes an exacerbated type 2 response in mouse strains with a gene knockout (KO) such that they lack IL‐12p40 (IL‐12KO mice). In contrast, type 1 responses are inhibited by TGF‐β without Th2 cell expansion in BALB/c mice infected with L. chagasi. We questioned whether the type 2 or the TGF‐β response would dominate during L. chagasi infection of IL‐12KO mice. C57BL/6 mice developed self‐resolving L. chagasi infection with abundant IFN‐γ. In contrast, L. chagasi disease was exacerbated and IFN‐γ was low in IL‐12KO mice. Total TGF‐β was significantly higher in IL‐12KO than control C57BL/6 mice, but IL‐4 and IL‐10 levels were similar. TGF‐β was further augmented in IL‐12/IFN‐γ double‐KO mice. Thus, in contrast to L. major, the TGF‐β response was exacerbated whereas type 2 cells were not expanded during L. chagasi infection of IL‐12KO mice. We conclude that L. chagasi has an inherent propensity to elicit a prominent TGF‐β response that either suppresses, or is suppressed by, a type 1 response. We propose this be termed a "type 3" immune response, which can antagonize a type 1 response.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

The TGF-? response toLeishmania chagasi in the absence of IL-12

et al. 2002

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“…Indeed, induction of IL-10 in CD4 + CD45RA + T cells, stimulated with anti-CD3 and anti-CD46 was shown to be reduced after addition of IL-12 [22]. Our data are comparable with the previously mentioned study in murine T cells, in which resembling skewing conditions were used [9]. The inhibitory effect of anti-IL-12 on TGF-b-mediated IL-10 secretion may indicate that IL-12 signalling interferes with the SMAD4 mediated pathway.…”

Section: Discussionsupporting

confidence: 91%

“…We demonstrate that the IL-10 secretion measured in T cells under Th2 polarizing conditions is not enhanced after stimulation with TGF-b. This is comparable to what was shown previously in murine CD4 + T cells, indicating that Th2 polarizing conditions make cells less sensitive to the effects of TGF-b [9,19]. A study performed in a HT-2 cell line (producing IL-10 but not IL-4 or IL-5) demonstrated that TGF-b-induced SMAD3 interacts with GATA-3 to form a complex which can up-regulate IL-10 expression [20].…”

Section: Discussionsupporting

confidence: 87%

The interleukin-10 inducing effect of transforming growth factor-β on human naive CD4+ T cells from cord blood is restricted to the TH1 subset

Kapitein

Tiemessen

Liu

et al. 2006

Clinical and Experimental Immunology

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Transforming growth factor (TGF-beta) seems to play a role in the regulation of immune responses, mainly by its suppressive function towards cells of the immune system. However, both in mice and human, conflicting data are published on the capacity of TGF-beta to induce interleukin (IL)-10 secretion in both naive and skewed T cell populations. Our aim was to test the IL-10-inducing capacity of TGF-beta in both naive and skewed cord blood mononuclear cells (CBMCs) and elucidate the mechanism by which TGF-beta exerts its effect. Therefore, naive CBMCs and CBMCs during skewing under T helper 1 (Th1) and Th2 polarizing conditions were stimulated with CD3 and/or CD28 in the presence or absence of TGF-beta. Proliferation, cytokine production and mRNA expression of transcription factors was measured. TGF-beta enhanced the IL-10 production in Th1 and naive cells only, and suppressed the T(H)1 phenotype as demonstrated in cytokine levels and T-box expression in T cells (T-bet) expression. Interestingly, forkhead box p3 (Foxp3) expression tended to increase in both Th1 and Th2 cells. These data indicate that TGF-beta can induce a regulatory phenotype in both naive and Th1-polarized cells derived from cord blood. The induction of IL-10 was not observed in Th2-polarized phenotype, indicating that TGF-beta might be especially of interest for immunomodulation in Th1 cells.

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“…Additionally, CD4 + CD25 + foxp3 + Tregs were detected in the lymph nodes 10 days following SVF treatment. The differential regulation of T cell subsets by alteration of the cytokine repertoire within the local environment is integral to the resulting immune responses . Although considered pro‐inflammatory by production of IFN‐γ, the differentiation of Th1 cells can suppress Th17 cells .…”

Section: Discussionmentioning

confidence: 99%

Adipose Stromal Vascular Fraction-Mediated Improvements at Late-Stage Disease in a Murine Model of Multiple Sclerosis

et al. 2016

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Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes. The SVF can be culture expanded to generate ASC lines. Clinical trials continue to demonstrate the safety and efficacy of ASC therapies for treating several diseases. However, little is known about the effectiveness of the SVF for neurodegenerative diseases, such as MS. At late-stage disease, EAE mice show severe motor impairment. The goal for these studies was to test the effectiveness of SVF cells and ASC in EAE mice after the onset of neuropathology. The clinical scoring, behavior, motor function, and histopathologic analyses revealed significant improvements in EAE mice treated with the SVF or ASC. Moreover, SVF treatment mediated more robust improvements to CNS pathology than ASC treatment based on significant modulations of inflammatory factors. The most pronounced changes following SVF treatment were the high levels of interleukin-10 in the peripheral blood, lymphoid and CNS tissues along with the induction of regulatory T cells in the lymph nodes which indicate potent immunomodulatory effects. The data indicate SVF cells effectively ameliorated the EAE immunopathogenesis and supports the potential use of SVF for treating MS. Stem Cells 2017;35:532-544.

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The effect of TGF-β1 on immune responses of naïve versus memory CD4+ Th1/Th2 T cells

Cited by 41 publications

References 0 publications

The TGF-? response toLeishmania chagasi in the absence of IL-12

The TGF-? response toLeishmania chagasi in the absence of IL-12

The interleukin-10 inducing effect of transforming growth factor-β on human naive CD4+ T cells from cord blood is restricted to the TH1 subset

Adipose Stromal Vascular Fraction-Mediated Improvements at Late-Stage Disease in a Murine Model of Multiple Sclerosis

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