Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production

Allan, Sarah; Crome, Sarah Q.; Crellin, Natasha K.; Passerini, Laura; Steiner, Theodore S.; Bacchetta, Rosa; Roncarolo, Maria Grazia; Levings, Megan K.

doi:10.1093/intimm/dxm014

Cited by 769 publications

(724 citation statements)

References 38 publications

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“…It is a transcription factor critical for the development and function of regulatory T cells [30][31][32][33], and its expression is generally considered to define Tregs with suppressive capability [31][32][33][34]. On the other hand, in recent studies it became clear that the role of human FOXP3 is different from that of its murine counterpart, being a consequence of activation status, and responsible for an anergic phenotype, but not necessarily for a regulatory function of cells that express it [4,26,28,[34][35][36]. Nevertheless, a suppressive capacity of CD4 + CD25 high FOXP3 + cells isolated from human tumors was demonstrated by Kryczek et al [37].…”

Section: Discussionmentioning

confidence: 99%

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

Ladányi

Mohos

Somlai

et al. 2010

Pathol. Oncol. Res.

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Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4 + CD25 + Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3 + cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3 + cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3 + lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma.

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Section: Discussionmentioning

confidence: 99%

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

Ladányi

Mohos

Somlai

et al. 2010

Pathol. Oncol. Res.

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“…Indeed a number of groups have noted a reduction of CD4 1 CD25 hi Treg in SLE [54,55]. FOXP3 expression is known to be increased upon activation of human T cells [56][57][58]. However, the increased numbers of CD4 1 FOXP3 1 T cells found in autoimmune inflammatory environments such as EAE or the rheumatoid joint [59][60][61] has been used to support the argument that Treg are expanded in inflammation but are unable to establish control [62].…”

Section: Discussionmentioning

confidence: 99%

Abnormal CTLA‐4 function in T cells from patients with systemic lupus erythematosus

et al. 2010

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CTLA‐4 is a critical gatekeeper of T‐cell activation and immunological tolerance and has been implicated in patients with a variety of autoimmune diseases through genetic association. Since T cells from patients with the autoimmune disease systemic lupus erythematosus (SLE) display a characteristic hyperactive phenotype, we investigated the function of CTLA‐4 in SLE. Our results reveal increased CTLA‐4 expression in FOXP3− responder T cells from patients with SLE compared with other autoimmune rheumatic diseases and healthy controls. However, CTLA‐4 was unable to regulate T‐cell proliferation, lipid microdomain formation and phosphorylation of TCR‐ζ following CD3/CD28 co‐stimulation, in contrast to healthy T cells. Although lupus T cells responded in vitro to CD3/CD28 co‐stimulation, there was no parallel increase in CTLA‐4 expression, which would normally provide a break on T‐cell proliferation. These defects were associated with exclusion of CTLA‐4 from lipid microdomains providing an anatomical basis for its loss of function. Collectively our data identify CTLA‐4 dysfunction as a potential cause for abnormal T‐cell activation in patients with SLE, which could be targeted for therapy.

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“…The follicular group was defined as the population of Foxp3 þ cells that mainly occupied lymphoid follicles of the submucosal layer compared to any other region of the tumour (original magnification: Â 4, Â 40). (Zheng et al, 2004;Fontenot et al, 2005;Allan et al, 2007;Pillai et al, 2007). Recently, it has been reported that Foxp3, forkhead/winged helix transcription factor, is the most reliable marker of T regs Yagi et al, 2004;Fontenot et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Localisation pattern of Foxp3+ regulatory T cells is associated with clinical behaviour in gastric cancer

et al. 2007

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It has been reported that the population of regulatory T cells (T regs) is increased in tumour-infiltrating lymphocytes in cancer-bearing hosts. Recently, forkhead/winged helix transcription factor p3, Foxp3, is thought to be the most reliable marker of T regs. In the present study, we investigated the prevalence and localisation pattern of Foxp3 þ cells in gastric cancer (n ¼ 80) by immunohistochemistry, in relation to the clinical outcome of gastric cancer patients. Immunohistochemical staining was performed with anti-Foxp3 mAb, and Foxp3 þ cells were semiquantified. We divided all cases into two groups: Foxp3 þ -high (n ¼ 40) and Foxp3 þ -low (n ¼ 40) groups, by the median size of the population of Foxp3 þ cells. Furthermore, in terms of the localisation pattern of accumulating Foxp3 þ cells in tumours, we classified all cases into three groups: a peri-tumour group (n ¼ 30), a diffuse group (n ¼ 40), and a follicular group (n ¼ 10). As a result, although the populations of Foxp3 þ cells in stage IV were significantly larger than those in stage I (Po0.05), there was no significant difference in survival between the patients with high and low population levels of Foxp3 þ cells. However, survival in patients with a diffuse pattern of Foxp3 þ cells was significantly poorer than in those with a peritumoral pattern. In conclusion, the localisation pattern, but not the population size, of Foxp3 þ cells was significantly related to patient survival.

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Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production

Cited by 769 publications

References 38 publications

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

FOXP3+ Cell Density in Primary Tumor Has No Prognostic Impact in Patients with Cutaneous Malignant Melanoma

Abnormal CTLA‐4 function in T cells from patients with systemic lupus erythematosus

Localisation pattern of Foxp3+ regulatory T cells is associated with clinical behaviour in gastric cancer

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