scholarly journals The fellowship of regulatory and tissue-resident memory cells

2021 ◽  
Author(s):  
Leandro Barros ◽  
Cristina Ferreira ◽  
Marc Veldhoen
Keyword(s):  
Communication Network ◽  
T Cells ◽  
Immune Surveillance ◽  
Treg Cells ◽  
Tissue Homeostasis ◽  
Lymphoid Tissues ◽  
Cancer Therapies ◽  
Immune Defence ◽  
Memory Cells ◽  
Cognate Antigen

AbstractT cells located in non-lymphoid tissues have come to prominence in recent years. CD8+ tissue-resident memory (Trm) cells are important for tissue immune surveillance, provide an important line of defence against invading pathogens and show promise in cancer therapies. These cells differ in phenotype from other memory populations, are adapted to the tissue they home to where they found their cognate antigen and have different metabolic requirements for survival and activation. CD4+ Foxp3+ regulatory T (Treg) cells also consist of specialised populations, found in non-lymphoid tissues, with distinct transcriptional programmes. These cells have equally adapted to function in the tissue they made their home. Both Trm and Treg cells have functions beyond immune defence, involving tissue homeostasis, repair and turnover. They are part of a multicellular communication network. Intriguingly, occupying the same niche, Treg cells are important in the establishment of Trm cells, which may have implications to harness the immune surveillance and tissue homeostasis properties of Trm cells for future therapies.

scholarly journals The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus

2001 ◽  
Vol 8 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Charles L. Hardy ◽  
Dale I. Godfrey ◽  
Roland Scollay
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Activated T Cells ◽  
Cell Pool ◽  
Peripheral Lymphoid Tissue ◽  
Cognate Antigen ◽  
Transgenic Cells ◽  
Peripheral Cells

Although the maturation and export of T cells from the thymus has been extensively studied, the movement of cells in the opposite direction has been less well documented. In particular, the question of whether T cells which have been activated by antigen in the periphery are more likely to return to the thymus had been raised but not clearly answered. We examined this issue by activating T cells present in the periphery with their cognate antigen, and assessing migration to the thymus. TCR-transgenic cells from OT-I mice (Thy1.2+), which recognise the ovalbumin peptide OVA257–264in the context of H-2Kb, were transferred into otherwise unmanipulated Thy1.1+C57BL/6 mice. Recipient mice were injected i.v. with 5μgpeptide (SIINFEKL) approximately 24 hours later. The numbers of donor-derived (Thy1.2+) cells in the thymus and peripheral lymphoid tissue were determined. The results clearly show increased numbers of transgenic cells in the thymus 3 days after antigenic stimulation. However, since numbers of transgenic cells increased in the spleen and LN in about the same proportion, the data do not support the notion that there is highly increased selective migration of activated T cells to the thymus. Rather, they suggest that a sample of peripheral cells enters the thymus each day, and that the mature immigrants detected in the thymus merely reflect the contents of the peripheral T cell pool.

scholarly journals Context-Dependent Effect of Glucocorticoids on the Proliferation, Differentiation, and Apoptosis of Regulatory T Cells: A Review of the Empirical Evidence and Clinical Applications

2019 ◽  
Vol 20 (5) ◽  
pp. 1142 ◽  
Author(s):  
Luigi Cari ◽  
Francesca De Rosa ◽  
Giuseppe Nocentini ◽  
Carlo Riccardi
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Inflammatory Diseases ◽  
Treg Cells ◽  
Cell Number ◽  
Lymphoid Tissues ◽  
Treg Number ◽  
Context Dependent

Glucocorticoids (GCs) are widely used to treat several diseases because of their powerful anti-inflammatory and immunomodulatory effects on immune cells and non-lymphoid tissues. The effects of GCs on T cells are the most relevant in this regard. In this review, we analyze how GCs modulate the survival, maturation, and differentiation of regulatory T (Treg) cell subsets into both murine models and humans. In this way, GCs change the Treg cell number with an impact on the mid-term and long-term efficacy of GC treatment. In vitro studies suggest that the GC-dependent expansion of Treg cells is relevant when they are activated. In agreement with this observation, the GC treatment of patients with established autoimmune, allergic, or (auto)inflammatory diseases causes an expansion of Treg cells. An exception to this appears to be the local GC treatment of psoriatic lesions. Moreover, the effects on Treg number in patients with multiple sclerosis are uncertain. The effects of GCs on Treg cell number in healthy/diseased subjects treated with or exposed to allergens/antigens appear to be context-dependent. Considering the relevance of this effect in the maturation of the immune system (tolerogenic response to antigens), the success of vaccination (including desensitization), and the tolerance to xenografts, the findings must be considered when planning GC treatment.

FOXP3 Expression in B and T Cell Lymphomas.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4503-4503
Author(s):  
Giovanna Roncador ◽  
Juan Fernando Garcia ◽  
Jose Francisco Garcia ◽  
Lorena Maestre ◽  
Elena Lucas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory Gene ◽  
Immune Surveillance ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Cell Leukaemia ◽  
Tissue Sections ◽  
T Cell Lymphomas ◽  
And Function

Abstract Foxp3, which encodes a forkhead/winged helix transcription factor designated Scurfin, is a key regulatory gene required for the development and function of regulatory CD4+CD25+ T cells (Treg), a subpopulation of T-cells specialized in maintaining the balance between immunity and tolerance. Humans with defects in the FOXP3 gene, develop strong activation of the immune system, leading to multiorgan autoimmune disease, allergies, inflammatory bowel disease and severe infections, collectively known as the IPEX syndrome (immune deregulation, polyendocrinopathy, enteropathy, X-linked inheritance syndrome) Because of the importance of FOXP3 in the development and function of Treg cells, and its potential use as a specific Treg marker, we have developed several monoclonal antibodies against FOXP3, for use on paraffin-embedded tissue sections and evaluated its expression in a large series (150 cases) of B- and T-cell lymphomas. In reactive lymphoid tissue, strong nuclear FOXP3 expression was observed in approximately 5% of interfollicular T-cells. FOXP3 expression in tumour cells was confined to most of Adult T-cell Leukaemia/Lymphoma (ATLL) cases (68%), with some variability in protein expression. In other lymphoma types, FOXP3 expression was only detected in the reactive T-cell background, and the number of FOXP3-positive reactive T-cells was variable, ranging from almost a complete absence (Burkitt’s lymphoma) to abundant infiltrate (common in follicular lymphoma). In conclusion, the availability of a FOXP3 monoclonal antibody, not only provides an important tool for the study of the development and function of Treg cells, but also represents a useful marker for the identification of ATLL cases in formalin-fixed paraffin-embedded tissue sections. The presence or absence of Treg cells in the tumour environment could also play a role in the immune surveillance of tumours, thus implying a potential additional value for the detection of this cell population in tumour samples.

scholarly journals Clonal Evolution of CD8+T Cell Responses against Latent Viruses: Relationship among Phenotype, Localization, and Function

2014 ◽  
Vol 89 (1) ◽  
pp. 568-580 ◽  
Author(s):  
Ester B. M. Remmerswaal ◽  
Paul L. Klarenbeek ◽  
Nuno L. Alves ◽  
Marieke E. Doorenspleet ◽  
Barbera D. C. van Schaik ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hcmv Infection ◽  
Clonal Evolution ◽  
Acute Infection ◽  
Cell Receptor ◽  
Lymphoid Tissues ◽  
The Novel ◽  
Memory Cells ◽  
Cell Pool

ABSTRACTHuman cytomegalovirus (hCMV) infection is characterized by a vast expansion of resting effector-type virus-specific T cells in the circulation. In mice, interleukin-7 receptor α (IL-7Rα)-expressing cells contain the precursors for long-lived antigen-experienced CD8+T cells, but it is unclear if similar mechanisms operate to maintain these pools in humans. Here, we studied whether IL-7Rα-expressing cells obtained from peripheral blood (PB) or lymph nodes (LNs) sustain the circulating effector-type hCMV-specific pool. Using flow cytometry and functional assays, we found that the IL-7Rα+hCMV-specific T cell population comprises cells that have a memory phenotype and lack effector features. We used next-generation sequencing of the T cell receptor to compare the clonal repertoires of IL-7Rα+and IL-7Rα−subsets. We observed limited overlap of clones between these subsets during acute infection and after 1 year. When we compared the hCMV-specific repertoire between PB and paired LNs, we found many identical clones but also clones that were exclusively found in either compartment. New clones that were found in PB during antigenic recall were only rarely identical to the unique LN clones. Thus, although PB IL-7Rα-expressing and LN hCMV-specific CD8+T cells show typical traits of memory-type cells, these populations do not seem to contain the precursors for the novel hCMV-specific CD8+T cell pool during latency or upon antigen recall. IL-7Rα+PB and LN hCMV-specific memory cells form separate virus-specific compartments, and precursors for these novel PB hCMV-specific CD8+effector-type T cells are possibly located in other secondary lymphoid tissues or are being recruited from the naive CD8+T cell pool.IMPORTANCEInsight into the self-renewal properties of long-lived memory CD8+T cells and their location is crucial for the development of both passive and active vaccination strategies. Human CMV infection is characterized by a vast expansion of resting effector-type cells. It is, however, not known how this population is maintained. We here investigated two possible compartments for effector-type cell precursors: circulating acute-phase IL-7Rα-expressing hCMV-specific CD8+T cells and lymph node (LN)-residing hCMV-specific (central) memory cells. We show that new clones that appear after primary hCMV infection or during hCMV reactivation seldom originate from either compartment. Thus, although identical clones may be maintained by either memory population, the precursors of the novel clones are probably located in other (secondary) lymphoid tissues or are recruited from the naive CD8+T cell pool.

scholarly journals Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3283-3292 ◽  
Author(s):  
Renata Mazzucchelli ◽  
Julie A. Hixon ◽  
Rosanne Spolski ◽  
Xin Chen ◽  
Wen Qing Li ◽  
...  
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Cytotoxic T Lymphocyte ◽  
Treg Cells ◽  
Lymphoid Tissues ◽  
Normal Numbers ◽  
Thymic Development ◽  
Interleukin 7 ◽  
Forkhead Box ◽  
Necrosis Factor

Abstract Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7Rα−/− mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte–associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7Rα−/− lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7Rα: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells.

scholarly journals Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

2011 ◽  
Vol 208 (5) ◽  
pp. 1015-1025 ◽  
Author(s):  
Yukari Ohmichi ◽  
Jotaro Hirakawa ◽  
Yasuyuki Imai ◽  
Minoru Fukuda ◽  
Hiroto Kawashima
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Specific Ige ◽  
Treg Cells ◽  
Lymphoid Tissues ◽  
Lymphocyte Homing ◽  
Double Knockout ◽  
High Endothelial Venules ◽  
Peripheral Node

Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4+CD25+ regulatory T cells (Treg cells). Compared with the homing of CD4+CD25− conventional T cells, the homing of CD4+CD25+ Treg cells to NALT was less dependent on the L-selectin–PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses.

Pre-Transplant Infusion of Donor CD4+ CD25+ T Cells Suppresses Host Anti-Donor MiHA-Specific CD8 T Cells and Facilitates Stable Mixed Chimerism Following MHC-Matched Allogeneic Marrow Transplant.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3254-3254
Author(s):  
Alwi M. Shatry ◽  
Robert B. Levy
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Cd8 T Cells ◽  
Treg Cells ◽  
Mixed Chimerism ◽  
Lymphoid Tissues ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Marrow

Abstract Surmounting the barrier mediated by host T cells against successful engraftment of MHC-matched allogeneic marrow is a crucial objective of hematopoietic stem cell transplant (HCT). We proposed that the ability of unmanipulated donor CD4+ CD25+ regulatory T cells (Tregs) to suppress activation of host effector CD8+ T cells would enhance donor HC engraftment between strains disparate for multiple minor HA (MiHA), and promote stable chimerism. C57BL/6 (H-2b, Ly9.1−) mice conditioned (5.5 Gy TBI) 24 hrs earlier, were transplanted with Tregs and TCD-BM from 129P3/J (H-2, Ly9.1+) mice. By four weeks post-HCT, the mean frequency of circulating donor-derived (total Ly9.1+) cells was 15.7 ± SE 5.9% in recipients of 4 × 106 TCD-BM + Tregs (4.5 × 105) compared to the absence of donor chimerism in recipients of allogeneic HCT only (0.3 ± 0.09%) - a finding also evident from the analysis of circulating donor B220+ cells (8.7 ± 3.0 vs. 0.2 ± 0.06%). Based on these findings, we hypothesized that pre-HCT infusion of Tregs into a lymphopenic, allogeneic host might enhance their facilitating function. Accordingly, Tregs (4 or 1.5 × 105) were transplanted 24hr. post-conditioning either 3 days prior to HCT or co-transplanted with (day 0) donor TCD-BM. The transplant was rejected in recipients not administered donor Tregs. The higher dose of Tregs administered pre-transplant or co-transplanted facilitated equivalent donor cell chimerism. In contrast, administration of 1.5 × 105 Tregs resulted in chimerism only when this donor population was infused 3 days prior to HCT (1.6±0.9%). To test the hypothesis that donor Tregs suppressed host anti-donor specific CD8 T cells, we monitored host CD8+ T cell responses to the immunodominant donor epitope H60 by tetramer staining (LTFNYRNL/Kb). One month post-HCT of TCD-BM alone, the frequency of circulating tetramer+ CD8+ cells in these recipients rejecting the marrow graft was clearly greater compared to the frequency in recipients of TCD-BM + Tregs which engrafted (p<0.0008). In contrast, the host anti-donor CD8 levels were not different between recipients of TCD-BM alone and TCD-BM + D.0 ’low dose’ Treg administration which failed to engraft (p>0.05). Notably, transplants using unmanipulated host Tregs failed to support engraftment. These findings illustrate that donor Tregs support chimerism via suppression of host anti-donor antigen-specific T cells. Finally, the persistence of donor cells in circulation as well as in lymphoid tissues 3 months post-HCT indicated that long-term, stable chimerism was established by this Treg administration regimen. In total, our results demonstrate that donor Tregs promote MHC-matched allogeneic marrow engraftment under conditions of reduced intensity conditioning and that the strategy of pre-HCT Treg infusion supports the notion that antigen driven expansion of donor anti-host reactive Treg cells prior to stem cell transplants can increase their efficacy to facilitate hematopoietic engraftment. Experiments to study transient vs. long-term engraftment and expansion of donor Treg cells are being examined.

scholarly journals Tissue Tregs and Maintenance of Tissue Homeostasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Qing Shao ◽  
Jian Gu ◽  
Jinren Zhou ◽  
Qi Wang ◽  
Xiangyu Li ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Adipose Tissue ◽  
Tissue Homeostasis ◽  
Lymphoid Tissues ◽  
Immune Homeostasis ◽  
Peripheral Tissues ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Visceral Adipose

Regulatory T cells (Tregs) specifically expressing Forkhead box P3 (Foxp3) play roles in suppressing the immune response and maintaining immune homeostasis. After maturation in the thymus, Tregs leave the thymus and migrate to lymphoid tissues or non-lymphoid tissues. Increasing evidence indicates that Tregs with unique characteristics also have significant effects on non-lymphoid peripheral tissues. Tissue-resident Tregs, also called tissue Tregs, do not recirculate in the blood or lymphatics and attain a unique phenotype distinct from common Tregs in circulation. This review first summarizes the phenotype, function, and cytokine expression of these Tregs in visceral adipose tissue, skin, muscle, and other tissues. Then, how Tregs are generated, home, and are attracted to and remain resident in the tissue are discussed. Finally, how an increased understanding of these tissue Tregs might guide clinical treatment is discussed.

scholarly journals Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4556-4565 ◽  
Author(s):  
Maria Nikolova ◽  
Jean-Daniel Lelievre ◽  
Matthieu Carriere ◽  
Armand Bensussan ◽  
Yves Lévy
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Effector Cell ◽  
Cd8 T Cell ◽  
Treg Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Memory Cells ◽  
Effector Cells

Abstract The balanced manifestation of effector functions and the generation of long-living memory cells is a hallmark of efficient CD8+ T-cell response. Accumulating data pinpoint CD4+ CD25high regulatory T (Treg) cells as a key factor for the inefficiency of CD8+ T-cell responses in viral persistence. Little is known about the effects of Treg cells on the homeostasis of healthy donor CD8+ T cells. The present study demonstrates that Treg cells exert differential effects on CD8+ T-cell subsets. Treg cells inhibited mostly the polyclonal proliferation of CD27− effector cells compared with CD27+ memory CD8+ T cells. Moreover, they inhibited the polyclonal and antigen-driven differentiation of memory cells into functional effectors as defined by IFN-γ secretion and induction of CD160 expression. Finally, Treg cells reduced the apoptosis of memory but not of effector and terminal effector cell populations. These effects were at least in part mediated by a decreased expression of PD-L1, but not of programmed death 1 (PD-1), on CD8+ T cells after activation. Thus, in the setting of a healthy immune system, Treg cells fine-tune the memory/effector cell balance and promote the accumulation of long-living memory cells in case of strong stimulation.

Sign in / Sign up

Export Citation Format

Share Document