Human CD45RA− FoxP3hi Memory-Type Regulatory T Cells Show Distinct TCR Repertoires With Conventional T Cells and Play an Important Role in Controlling Early Immune Activation

Lei, Hong; Kuchenbecker, Léon; Streitz, Mathias; Sawitzki, Birgit; Vogt, Katrin; Landwehr-Kenzel, Sybille; Millward, Jason M.; Juelke, Kerstin; Babel, Nina; Neumann, Avidan U.; Reinke, Petra; Volk, Hans‐Dieter

doi:10.1111/ajt.13315

Cited by 30 publications

(33 citation statements)

References 45 publications

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“…We recently demonstrated that about 10% Treg in the peripheral blood of healthy donors and patients awaiting for kidney transplantation express an effector-memory phenotype (CD45RA – CD62L – ) allowing migration into inflamed tissues without further activation (Figure 2A ). Upon in vitro expansion, a significant proportion of both naïve (CD45RA + CD62L + ) and central-memory (CD45RA – CD62L + ) Treg shift their phenotype into effector-memory like (Figure 2B ), which could facilitate further migration of Treg into tissues when the expanded Treg products are transferred into patients ( Lei et al, 2015 ).…”

Section: Homing and Accumulation Of Tregs At Sites Of Injurymentioning

confidence: 99%

Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners

et al. 2015

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Regulatory T cells (Tregs) offer new immunotherapeutic options to control undesired immune reactions, such as those in transplant rejection and autoimmunity. In addition, tissue repair and regeneration depend on a multitude of tightly regulated immune and non-immune cells and signaling molecules. There is mounting evidence that adequate innate responses, and even more importantly balanced adaptive immune responses, are key players in the tissue repair and regeneration processes, even in absence of any immune-related disease or infection. Thus, the anti-inflammatory and anti-apoptotic capacities of Treg can affect not only the effector immune response, creating the appropriate immune environment for successful tissue repair and regeneration, but growing evidence shows that they also have direct effects on tissue cell functions. Here we summarize the present views on how Treg might support tissue regeneration by direct control of undesired immune reactivity and also by direct interaction with non-immune tissue cells. We describe tissue-resident Treg and their specific phenotypes in skin, visceral adipose tissue, and skeletal muscle. In addition, we touch on the topic of osteoimmunology, discussing the direct interactions of Treg with bone-forming cells, such as osteoblasts and their mesenchymal stromal cell (MSC) progenitors—a field which is under-investigated. We hypothesize a cross-talk between Treg and bone-forming cells through the CD39–CD73-(adenosine)-adenosine receptor pathway, which might also potentiate the differentiation of MSCs, thus facilitating bone regeneration. This hypothesis may provide a road map for further investigations on the cross-talk between the immune and the skeletal system, and also enable the development of better strategies to promote bone repair and regeneration.

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Section: Homing and Accumulation Of Tregs At Sites Of Injurymentioning

confidence: 99%

Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners

et al. 2015

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“…Several investigators confirmed that isolation of T cells with high expression of CD25 and low expression of CD127 will result in a highly purified population of Tregs with suppressive capacities in functional assays . Other markers that have been associated with (certain subsets of) Tregs are Helios, CTLA‐4, CD45RA/RO, CD62L, C‐C chemokine receptor type 6 (CCR6) and CD39 . Tregs are comprised of two main populations: thymus‐derived natural Tregs and peripherally generated‐induced Tregs .…”

Section: Regulatory T Cells: Phenotype and Functionmentioning

confidence: 99%

What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

Craenmehr

Heidt

Eikmans

et al. 2016

HLA

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Couples of whom the woman has had a miscarriage have two major concerns: the cause and possible risk of recurrence. Unfortunately, a significant proportion of cases of recurrent miscarriage (RM) remain unexplained despite detailed investigation. Because data suggest that regulatory T cells (Treg) are involved in the maternal acceptance of the allogeneic foetus, RM could possibly be explained by a disturbance of the Treg network. The possible role of Tregs in RM is described in this review, as well as their potential application in diagnostics and therapeutic intervention trials.

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“…They belong to a subpopulation of CD4 + cells, constituting 5-10% of peripheral T cells, and are proclaimed as masters and regulators of the immune response (11). Recent data suggest that regulatory T (T reg) cells not only control autoimmunity, but also play a key role in maintaining the intratissue immune balance, particularly after challenges of tissue homeostasis that trigger inflammatory processes, such as infections, ischemia, or trauma (12).…”

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confidence: 99%

Immunomodulation by adoptive regulatory T‐cell transfer improves Coxsackievirus B3‐induced myocarditis

et al. 2018

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Regulatory T (T) cells offer new therapeutic options for controlling undesired systemic and local immune responses. The aim of the current study was to determine the impact of therapeutic T administration on systemic and cardiac inflammation and remodeling in coxsackievirus B3 (CVB3) -induced myocarditis. Therefore, syngeneic T cells were applied intravenously in CVB3-infected mice 3 d after infection. Compared with CVB3 + PBS mice, CVB3 + T mice exhibited lower left ventricular (LV) chemokine expression, accompanied by reduced cardiac presence of proinflammatory Ly6CCCR2Cx3Cr1 monocytes and higher retention of proinflammatory Ly6CCCR2Cx3Cr1 monocytes in the spleen. In addition, splenic myelopoiesis was reduced in CVB3 + T compared with CVB3 + PBS mice. Coculture of T cells with splenocytes isolated from mice 3 d post-CVB3 infection further demonstrated the ability of T cells to modulate monocyte differentiation in favor of the anti-inflammatory Ly6CCCR2Cx3Cr1 subset. T-mediated immunomodulation was paralleled by lower collagen 1 protein expression and decreased levels of soluble and insoluble collagen in LV of CVB3 + T compared with CVB3 + PBS mice. In agreement with these findings, LV systolic and diastolic function was improved in CVB3 + T mice compared with CVB3 + PBS mice. In summary, adoptive T transfer in the inflammatory phase of viral-induced myocarditis protects the heart against inflammatory damage and fibrosis via modulation of monocyte subsets.-Pappritz, K., Savvatis, K., Miteva, K., Kerim, B., Dong, F., Fechner, H., Müller, I., Brandt, C., Lopez, B., González, A., Ravassa, S., Klingel, K., Diez, J., Reinke, P., Volk, H.-D., Van Linthout, S., Tschöpe, C. Immunomodulation by adoptive regulatory T-cell transfer improves Coxsackievirus B3-induced myocarditis.

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Human CD45RA− FoxP3hi Memory-Type Regulatory T Cells Show Distinct TCR Repertoires With Conventional T Cells and Play an Important Role in Controlling Early Immune Activation

Cited by 30 publications

References 45 publications

Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners

Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners

What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

Immunomodulation by adoptive regulatory T‐cell transfer improves Coxsackievirus B3‐induced myocarditis

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