Characterization of IL-10-Secreting T Cells Derived from Regulatory CD4+CD25+ Cells by the TIRC7 Surface Marker

Wakkach, Abdelilah; Augier, Séverine; Breittmayer, Jean‐Philippe; Blin-Wakkach, Claudine; Carle, Georges F.

doi:10.4049/jimmunol.180.9.6054

Cited by 19 publications

(21 citation statements)

References 45 publications

(54 reference statements)

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“…During tumor progression, Tregs accumulate in tumors and secondary lymphoid organs (18,28). It has been suggested that the CCL22 produced by tumor cells or associated macrophages recruits Tregs into the tumor bed (39).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Blood Monocytes Contribute to Tumor Development and Represent a Privileged Target To Improve Host Immunosurveillance

Augier

Luci

Carle

et al. 2010

The Journal of Immunology

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Progressing tumors in humans and mice are frequently infiltrated by a highly heterogeneous population of inflammatory myeloid cells that contribute to tumor growth. Among these cells, inflammatory Gr-1+ monocytes display a high developmental plasticity in response to specific microenvironmental signals, leading to diverse immune functions. These observations raise the question of the immune mechanisms by which inflammatory monocytes may contribute to tumor development. In this study, we found that adoptive transfer of normal inflammatory Gr-1+ monocytes in tumor-bearing mice promotes tumor growth. In this tumoral environment, these monocytes can differentiate into tolerogenic dendritic cells (DCs) that produce IL-10 and potently induce regulatory T cell responses in vivo. Moreover, diverting the differentiation of Gr-1+ monocytes into tolerogenic DCs by forced expression of IL-10 soluble receptor and IL-3 in tumor cells improves host immunosurveillance by reducing the regulatory T cell frequency and by inducing immunogenic DCs in the tumor. As a consequence, tumor growth is strongly reduced. Our findings indicate that Gr-1+ monocytes represent a valuable target for innovative immunotherapeutic strategies against cancer.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Blood Monocytes Contribute to Tumor Development and Represent a Privileged Target To Improve Host Immunosurveillance

Augier

Luci

Carle

et al. 2010

The Journal of Immunology

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“…ϩ monocytes/macrophages and CD4 ϩ CD25 ϩ T cells Monocyte/macrophages have been implicated as the cellular source of IL-10 in measles patients (37), and recent studies have shown that CD4 ϩ CD25 ϩ Treg secrete IL-10 and can be a major mediator of immune suppression in infection (38,39). To determine whether CD14 ϩ monocyte/macrophages and/or CD4 ϩ CD25 ϩ T cells could be responsible for the elevated plasma IL-10, and whether MV treatment results in an increase in their cell number, we treated PBMC from healthy donors with MV (MOI ϭ 1) or Vero-SLAM cell lysate (mock) followed 3 days later by PMA, ionomycin, and brefeldin A stimulation for 3 h before FACS analysis (Fig.…”

Section: Up-regulates Il-10-producing Cd14mentioning

confidence: 99%

Measles Virus Infection in Adults Induces Production of IL-10 and Is Associated with Increased CD4+CD25+ Regulatory T Cells

Cheng

Shi

et al. 2008

The Journal of Immunology

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Despite steady progress in elimination of measles virus globally, measles infection still causes 500,000 annual deaths, mostly in developing countries where endemic measles strains still circulate. Many adults are infected every year in China, with symptoms more severe than those observed in children. In this study, we have used blood samples from adult measles patients in Shanghai and age-matched healthy controls to gain an understanding of the immune status of adult measles patients. IFN-α mRNA was reduced in patient PBMC compared with healthy controls. In contrast, gene expression and plasma production of IL-2, IL-10, and IFN-γ were elevated in patient blood. A similar cytokine profile was observed at early times when cultured PBMC were infected with a clinical isolate of measles virus. In contrast to previous studies in pediatric patients, we did not find a reduction in total CD4+ and CD8+ T cells in patient PBMC. Interestingly, we found that CD4+CD25+CD127low regulatory T cells were significantly increased in patient PBMC compared with controls. Using intracellular cytokine staining we also show that the measles virus induces IL-10-producing CD14+ and CD4+CD25+ cells in PBMC. Our results show that adult measles patients in the acute phase of the disease have a mixed Th1/Th2 type response, accompanied with severe immunosuppression of both innate and adaptive responses including suppression of type I IFN. Both regulatory T cells and plasma IL-10 may contribute to the immunosuppression.

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“…In addition to a3, the Tcirg1 gene mutated in oc/oc mice encodes another protein called TIRC7 and representing, in mouse, a marker of regulatory T-cell subsets. 49 However, because expression of TIRC7 and distribution of TIRC7 ϩ regulatory T cells are not altered in oc/oc mice (A.W., unpublished data, 2006), it is doubtful that the Tcirg1 mutation directly affects T-cell phenotype. More probably, this Th17 phenotype could result from the modifications of the bone microenvironment and cellular interactions resulting from osteopetrosis.…”

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Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts

Wakkach

Mansour

Dacquin

et al. 2008

Blood

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IntroductionAn increasing number of studies underline the interactions between the bone and immune systems and have led to the emergence of osteoimmunology. 1,2 Excessive bone resorption is frequently associated with chronic infections and autoimmune and inflammatory diseases. [3][4][5][6] The immune system plays a major role in this process, in particular through activated T cells, which secrete proinflammatory cytokines involved in osteoclastogenesis. 7 However, less is known about the involvement of other immune cells in the control of bone resorption. Dendritic cells (DCs) also play an important role in autoimmune and inflammatory diseases. 8 These cells derive from the same myeloid precursor as osteoclasts (OCLs), and both cell types are modulated by common factors, mainly by receptor activator of NF-B ligand (RANK-L). RANK-L is essential for the differentiation of OCLs, 9 the activity and survival of DCs. 10 These data highlight a potential link between DCs and OCLs.Cells from the myelomonocytic lineage, including DCs, display a high developmental and functional plasticity depending on local factors and stimuli experienced during their differentiation and maturation. 11,12 Although they were considered to be terminally differentiated cells, recent studies have suggested that mature splenic DCs can be influenced by their microenvironment to undergo further differentiation. Splenic stromal cells induce mature DCs to differentiate into regulatory DCs, which differ from mature DCs by their phenotype, their cytokine secretion pattern, and their ability to inhibit T-cell proliferation. 13 Moreover, DCs generated in vitro transdifferentiate into endothelial cells when cultured with tumor-conditioned media 14 or into OCLs when cultured with osteoclastogenic factors. 15,16 Although these in vitro studies revealed the capacity of DCs to transdifferentiate into other cell types under specific conditions, it is not clear yet whether this plasticity takes place in vivo.Osteopetrosis is characterized by an impaired bone resorption because of the absence of OCL formation or activity. 17 In the osteopetrotic oc/oc mouse, differentiated OCLs are present but are unable to resorb bone because of a deletion in the Tcirg1 gene encoding the a3 subunit of the vacuolar ATPase. 18 The a3 protein is responsible for the acidification process necessary for the dissolution of the bone matrix leading to the formation of resorption lacunae. In the absence of a3 expression, the bone marrow of oc/oc mice is filled with numerous and disorganized trabeculae, and osteoclastogenesis is highly increased. 19,20 The consequence of this severe osteopetrotic phenotype is a life span less than 3 weeks. Therefore, the oc/oc mouse provides an appropriate model to assess the in vivo capacity of wild-type precursor cells to give rise to functional OCLs.To assess whether DCs have an osteoclastogenic potential, we purified them from normal mice and cultured them with RANK-L and macrophage-colony stimulating factor (M-CSF). We showed that this treatment a...

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Characterization of IL-10-Secreting T Cells Derived from Regulatory CD4+CD25+ Cells by the TIRC7 Surface Marker

Cited by 19 publications

References 45 publications

Inflammatory Blood Monocytes Contribute to Tumor Development and Represent a Privileged Target To Improve Host Immunosurveillance

Inflammatory Blood Monocytes Contribute to Tumor Development and Represent a Privileged Target To Improve Host Immunosurveillance

Measles Virus Infection in Adults Induces Production of IL-10 and Is Associated with Increased CD4+CD25+ Regulatory T Cells

Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts

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