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 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.

scholarly journals Cytotoxic-T-Lymphocyte-Associated Antigen 4 Blockade Abrogates Protection by Regulatory T Cells in a Mouse Model of Microbially Induced Innate Immune-Driven Colitis

2008 ◽  
Vol 76 (12) ◽  
pp. 5834-5842 ◽  
Author(s):  
Koichiro Watanabe ◽  
Varada P. Rao ◽  
Theofilos Poutahidis ◽  
Barry H. Rickman ◽  
Masahiro Ohtani ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Treg Cell ◽  
T Lymphocyte ◽  
Bacterial Infections ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Treg Cells ◽  
Innate Immune ◽  
Cell Transfer

ABSTRACT Cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) expressed at high levels by CD4+ CD25+ CD45RBlow regulatory T cells (Treg) is essential to their homeostatic and immunoregulatory functions. However, its relevance to anti-inflammatory roles of Treg in the context of colitogenic innate immune response during pathogenic bacterial infections has not been examined. We showed earlier in Rag2-deficient 129/SvEv mice that Treg cells are capable of suppressing colitis and colon cancer triggered by Helicobacter hepaticus, a widespread murine enterohepatic pathogen. Using this model, we now examined the effects of antibody blockade of CTLA-4 on Treg function during innate immune inflammatory response. Consistent with our previous findings, we found that a single adoptive transfer of Treg cells prior to infection prevented colitis development despite persistent H. hepaticus infection in recipient mice. However, when infected mice were injected with anti-CTLA-4 antibody along with Treg cell transfer, they developed a severe acute colitis with poor body condition that was not observed in Rag2−/− mice without Treg cell transfer. Despite high numbers of Foxp3+ Treg cells, evident by immunohistochemical analyses in situ, the CTLA-4 antibody-treated mice had severely inflamed colonic mucosa and increased rather than decreased expression levels of cytokines gamma interferon and interleukin-2. These findings indicate that antibody blockade of CTLA-4 clearly abrogates Treg cell ability to suppress innate immune-driven colitis and suggest that Treg cell CTLA-4 cognate interactions may be necessary to maintain homeostasis among cells of innate immunity.

scholarly journals FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4953-4960 ◽  
Author(s):  
Mojgan Ahmadzadeh ◽  
Aloisio Felipe-Silva ◽  
Bianca Heemskerk ◽  
Daniel J. Powell ◽  
John R. Wunderlich ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Metastatic Melanoma ◽  
Treg Cell ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Production Capacity ◽  
Biological Marker ◽  
Foxp3 Expression ◽  
Treg Cells

Abstract Regulatory T (Treg) cells are often found in human tumors; however, their functional characteristics have been difficult to evaluate due to low cell numbers and the inability to adequately distinguish between activated and Treg cell populations. Using a novel approach, we examined the intracellular cytokine production capacity of tumor-infiltrating T cells in the single-cell suspensions of enzymatically digested tumors to differentiate Treg cells from effector T cells. Similar to Treg cells in the peripheral blood of healthy individuals, tumor-infiltrating FOXP3+CD4 T cells, unlike FOXP3− T cells, were unable to produce IL-2 and IFN-γ upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human Treg cells even in the tumor microenvironment. Accordingly, we enumerated FOXP3+CD4 Treg cells in intratumoral and peritumoral sections of metastatic melanoma tumors and found a significant increase in proportion of FOXP3+CD4 Treg cells in the intratumoral compared with peritumoral areas. Moreover, their frequencies were 3- to 5-fold higher in tumors than in peripheral blood from the same patients or healthy donors, respectively. These findings demonstrate that the tumor-infiltrating CD4 Treg cell population is accurately depicted by FOXP3 expression, they selectively accumulate in tumors, and their frequency in peripheral blood does not properly reflect tumor microenvironment.

517 Regulatory T cell functional identity is sustained by a glucose:lactate axis that is exploited in the tumor microenvironment

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A553-A553
Author(s):  
McLane Watson ◽  
Paolo Vignali ◽  
Steven Mullet ◽  
Abigail Overacre-Delgoffe ◽  
Ronal Peralta ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Treg Cell ◽  
High Glucose ◽  
Cell Function ◽  
Treg Cells ◽  
Effector T Cells ◽  
Flux Analysis ◽  
Major Barrier ◽  
Suppressive Function

BackgroundRegulatory T (Treg) cells are vital for preventing autoimmunity but are a major barrier to robust cancer immunity as the tumor microenvironment (TME) recruits and promotes their function. The deregulated cellular metabolism of tumor cells leads to a metabolite-depleted, hypoxic, and acidic TME. While the TME impairs the effector function of highly glycolytic tumor infiltrating CD8 T cells, Treg cell suppressive function is maintained. Further, studies of in vitro induced and ex vivo Treg cells reveal a distinct metabolic profile compared to effector T cells. Thus, it may be that the altered metabolic landscape of the TME and the increased activity of intratumoral Treg cells are linked.MethodsFlow cytometry, isotopic flux analysis, Foxp3 driven Cre-lox, glucose tracers, Seahorse extracellular flux analysis, RNA sequencing.ResultsHere we show Treg cells display heterogeneity in terms of their glucose metabolism and can engage an alternative metabolic pathway to maintain their high suppressive function and proliferation within the TME and other tissues. Tissue derived Treg cells (both at the steady state and under inflammatory conditions) show broad heterogeneity in their ability to take up glucose. However, glucose uptake correlates with poorer suppressive function and long-term functional stability, and culture of Treg cells in high glucose conditions decreased suppressive function. Treg cells under low glucose conditions upregulate genes associated with the uptake and metabolism of the glycolytic end-product lactic acid. Treg cells withstand high lactate conditions, and lactate treatment prevents the destabilizing effects of high glucose culture. Treg cells utilize lactate within the TCA cycle and generate phosphoenolpyruvate (PEP), a critical intermediate that can fuel intratumoral Treg cell proliferation in vivo. Using mice with a Treg cell-restricted deletion of lactate transporter Slc16a1 (MCT1) we show MCT1 is dispensable for peripheral Treg cell function but required intratumorally, resulting in slowed tumor growth and prolonged survival.ConclusionsThese data support a model in which Treg cells are metabolically flexible such that they can utilize ‘alternative’ metabolites present in the TME to maintain their suppressive identity. Further, our studies support the notion that tumors avoid immune destruction not only by depriving effector T cells of essential nutrients, but also by metabolically supporting regulatory T cells.

scholarly journals Transient Depletion of Foxp3+ Regulatory T Cells Selectively Promotes Aggressive β Cell Autoimmunity in Genetically Susceptible DEREG Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Deepika Watts ◽  
Marthe Janßen ◽  
Mangesh Jaykar ◽  
Francesco Palmucci ◽  
Marc Weigelt ◽  
...  
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Autoimmune Diabetes ◽  
Cell Activity ◽  
Spontaneous Diabetes ◽  
Nod Mice ◽  
Treg Cells ◽  
Β Cell ◽  
Cell Ablation ◽  
Tcr Repertoire

Type 1 diabetes (T1D) represents a hallmark of the fatal multiorgan autoimmune syndrome affecting humans with abrogated Foxp3+ regulatory T (Treg) cell function due to Foxp3 gene mutations, but whether the loss of Foxp3+ Treg cell activity is indeed sufficient to promote β cell autoimmunity requires further scrutiny. As opposed to human Treg cell deficiency, β cell autoimmunity has not been observed in non-autoimmune-prone mice with constitutive Foxp3 deficiency or after diphtheria toxin receptor (DTR)-mediated ablation of Foxp3+ Treg cells. In the spontaneous nonobese diabetic (NOD) mouse model of T1D, constitutive Foxp3 deficiency did not result in invasive insulitis and hyperglycemia, and previous studies on Foxp3+ Treg cell ablation focused on Foxp3DTR NOD mice, in which expression of a transgenic BDC2.5 T cell receptor (TCR) restricted the CD4+ TCR repertoire to a single diabetogenic specificity. Here we revisited the effect of acute Foxp3+ Treg cell ablation on β cell autoimmunity in NOD mice in the context of a polyclonal TCR repertoire. For this, we took advantage of the well-established DTR/GFP transgene of DEREG mice, which allows for specific ablation of Foxp3+ Treg cells without promoting catastrophic autoimmune diseases. We show that the transient loss of Foxp3+ Treg cells in prediabetic NOD.DEREG mice is sufficient to precipitate severe insulitis and persistent hyperglycemia within 5 days after DT administration. Importantly, DT-treated NOD.DEREG mice preserved many clinical features of spontaneous diabetes progression in the NOD model, including a prominent role of diabetogenic CD8+ T cells in terminal β cell destruction. Despite the severity of destructive β cell autoimmunity, anti-CD3 mAb therapy of DT-treated mice interfered with the progression to overt diabetes, indicating that the novel NOD.DEREG model can be exploited for preclinical studies on T1D under experimental conditions of synchronized, advanced β cell autoimmunity. Overall, our studies highlight the continuous requirement of Foxp3+ Treg cell activity for the control of genetically pre-installed autoimmune diabetes.

scholarly journals Graded RhoA GTPase Expression in Treg Cells Distinguishes Tumor Immunity From Autoimmunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Khalid W. Kalim ◽  
Jun-Qi Yang ◽  
Vishnu Modur ◽  
Phuong Nguyen ◽  
Yuan Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Treg Cell ◽  
Tumor Immunity ◽  
Th17 Cell ◽  
Treg Cells ◽  
Effector T Cells ◽  
Conditional Knockout ◽  
Cell Plasticity ◽  
Cell Homeostasis

RhoA of the Rho GTPase family is prenylated at its C-terminus. Prenylation of RhoA has been shown to control T helper 17 (Th17) cell-mediated colitis. By characterizing T cell-specific RhoA conditional knockout mice, we have recently shown that RhoA is required for Th2 and Th17 cell differentiation and Th2/Th17 cell-mediated allergic airway inflammation. It remains unclear whether RhoA plays a cell-intrinsic role in regulatory T (Treg) cells that suppress effector T cells such as Th2/Th17 cells to maintain immune tolerance and to promote tumor immune evasion. Here we have generated Treg cell-specific RhoA-deficient mice. We found that homozygous RhoA deletion in Treg cells led to early, fatal systemic inflammatory disorders. The autoimmune responses came from an increase in activated CD4+ and CD8+ T cells and in effector T cells including Th17, Th1 and Th2 cells. The immune activation was due to impaired Treg cell homeostasis and increased Treg cell plasticity. Interestingly, heterozygous RhoA deletion in Treg cells did not affect Treg cell homeostasis nor cause systemic autoimmunity but induced Treg cell plasticity and an increase in effector T cells. Importantly, heterozygous RhoA deletion significantly inhibited tumor growth, which was associated with tumor-infiltrating Treg cell plasticity and increased tumor-infiltrating effector T cells. Collectively, our findings suggest that graded RhoA expression in Treg cells distinguishes tumor immunity from autoimmunity and that rational targeting of RhoA in Treg cells may trigger anti-tumor T cell immunity without causing autoimmune responses.

scholarly journals Immunosenescence: a key player in cancer development

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Jingyao Lian ◽  
Ying Yue ◽  
Weina Yu ◽  
Yi Zhang
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Malignant Tumors ◽  
Killer Cell ◽  
Antibody Therapy ◽  
The Elderly ◽  
Mtor Inhibition ◽  
Interleukin 7 ◽  
The Many

Abstract Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.

scholarly journals Role of regulatory T cells in experimental autoimmune glomerulonephritis

2019 ◽  
Vol 316 (3) ◽  
pp. F572-F581 ◽  
Author(s):  
Stefanie Klinge ◽  
Karsten Yan ◽  
Daniel Reimers ◽  
Karen-Maria Brede ◽  
Joanna Schmid ◽  
...  
Keyword(s):  
T Cells ◽  
Crescentic Glomerulonephritis ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Rapid Loss ◽  
Type Iv ◽  
Forkhead Box ◽  
Goodpasture Antigen ◽  
Experimental Autoimmune

Anti-glomerular basement membrane (anti-GBM) disease is characterized by antibodies and T cells directed against the Goodpasture antigen, the noncollagenous domain of the α3-chain of type IV collagen [α3(IV)NC1] of the GBM. Consequences are the deposition of autoantibodies along the GBM and the development of crescentic glomerulonephritis (GN) with rapid loss of renal function. Forkhead box protein P3 (Foxp3)+ regulatory T (Treg) cells are crucial for the maintenance of peripheral tolerance to self-antigens and the prevention of immunopathology. Here, we use the mouse model of experimental autoimmune GN to characterize the role of Treg cells in anti-GBM disease. Immunization of DBA/1 mice with α3(IV)NC1 induced the formation of α3(IV)NC1-specific T cells and antibodies and, after 8–10 wk, the development of crescentic GN. Immunization resulted in increased frequencies of peripheral Treg cells and renal accumulation of these cells in the stage of acute GN. Depletion of Treg cells during immunization led to enhanced generation of α3(IV)NC1-specific antibodies and T cells and to aggravated GN. In contrast, depletion or expansion of the Treg cell population in mice with established autoimmunity had only minor consequences for renal inflammation and did not alter the severity of GN. In conclusion, our results indicate that in anti-GBM disease, Treg cells restrict the induction of autoimmunity against α3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has been established.

scholarly journals Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells

2015 ◽  
Vol 26 (15) ◽  
pp. 2845-2857 ◽  
Author(s):  
Magdalena Walecki ◽  
Florian Eisel ◽  
Jörg Klug ◽  
Nelli Baal ◽  
Agnieszka Paradowska-Dogan ◽  
...  
Keyword(s):  
T Cells ◽  
Androgen Receptor ◽  
Treg Cell ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Strong Increase ◽  
Histone H4 ◽  
And Function

CD4+CD25+Foxp3+ regulatory T (Treg) cells are able to inhibit proliferation and cytokine production in effector T-cells and play a major role in immune responses and prevention of autoimmune disease. A master regulator of Treg cell development and function is the transcription factor Foxp3. Several cytokines, such as TGF-β and IL-2, are known to regulate Foxp3 expression as well as methylation of the Foxp3 locus. We demonstrated previously that testosterone treatment induces a strong increase in the Treg cell population both in vivo and in vitro. Therefore we sought to investigate the direct effect of androgens on expression and regulation of Foxp3. We show a significant androgen-dependent increase of Foxp3 expression in human T-cells from women in the ovulatory phase of the menstrual cycle but not from men and identify a functional androgen response element within the Foxp3 locus. Binding of androgen receptor leads to changes in the acetylation status of histone H4, whereas methylation of defined CpG regions in the Foxp3 gene is unaffected. Our results provide novel evidence for a modulatory role of androgens in the differentiation of Treg cells.

Regulation of Hematopoietic Colony Forming Cells by CD4+CD25+ T Cells: A Role for T Regulatory Cells in Hematopoiesis?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3181-3181
Author(s):  
Maite Urbieta ◽  
Isabel Barao ◽  
Monica Jones ◽  
William J. Murphy ◽  
Robert B. Levy
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
T Cell ◽  
Treg Cell ◽  
Mhc Class Ii ◽  
Progenitor Cell ◽  
Cell Activity ◽  
Class Ii ◽  
Treg Cells

Abstract CD4+CD25+ T cells (Treg) comprise a small population within the normal peripheral CD4 T cell compartment. Their primary physiological role appears to be the regulation of autoimmune responses, however, in recent years it has been established that they can modulate anti-tumor as well as transplantation responses. Treg cells have been found to exert their affects on multiple types of immunologically relevant cells including CD4, CD8 and NK populations. Although model dependent, cytokines including TGFβ and IL-10 have been identified as mediators of this population’s regulatory activity and ex-vivo, the inhibition effected is generally contact dependent. Based upon the expanding application of Treg cells in stem cell transplants for the control of GVHD, rejection (HVG) and GVL responses, we hypothesized that following T cell receptor engagement and activation in recipients, CD4+CD25+ cells may modulate hematopoietic responses via production of effector cytokines. To address this question, various populations of CD4+CD25+ T cells were initially co-cultured with unfractionated syngeneic bone marrow cells (BMC) for 24–48 hours in medium supplemented with growth factors to maintain progenitor cell (i.e. CFU) function. Following co-culture, cells were collected and replated in triplicate in methylcellulose containing medium together with hematopoietic growth factors and five-seven days later, colonies were counted. CD4+CD25+ T cells were purified from BALB/c or B6–CD8−/− mice which were then activated for 3–8 days with anti-CD3/CD28 beads (a gift of Dr. B. Blazar, U. Minn.) These cells inhibited syngeneic CFU-IL3 colony ($25 cells) formation at ratios as low as 2:1 and 0.5:1 CD4+CD25+: BMC. Notably, Tregs from B6-CD8−/− mice exhibited comparable inhibition of allogeneic (BALB/c) CFU-IL3. Non-activated CD4+CD25+ T cells co-cultured with BMC did not exhibit this inhibitory activity nor did CD4+CD25− cells which contaminated (<10%) CD4+CD25+ populations. Activated Treg cells were also found to inhibit the production of CFU-HPP, a multi-potential marrow progenitor cell population. Contact dependency was found to be required for this effect as separation of activated CD4+CD25+ T cells from BMC “targets” in trans-well cultures abrogated inhibition. Prior depletion of CD25+ cells in vivo resulted in increases in CFU-GM 7–9 days after syngeneic BMT in mice suggesting that Tregs can inhibit hematopoietic reconstitution in vivo. To examine a potential contribution of TGFβ in this model, neutralizing anti-TGFβ mab was added during CD4+CD25+ T cell + BMC co-culture. The inhibition of CFU activity was abrogated in the presence of this antibody. To begin investigating the role of MHC class II molecules in this Treg cell activity, c-kit+ enriched (>85%) BMC from B6-MHC class II KO and B6-wt mice were co-cultured with B6 Treg cells from CD8−/− mice. In contrast to B6-wt c-kit enriched populations, CFU inhibition was not detected against the MHC class II deficient c-kit enriched BMC population. Antibody experiments are in progress to determine if cognate interaction is required between c-kit enriched cells and CD4+CD25+ T cells. In summary, this is the first report demonstrating that CD4+CD25+ T cells can alter hematopoietic progenitor cell activity. We hypothesize that membrane bound TGFβ may participate in effecting such regulation via direct Treg cell interactions with progenitor cell populations.

Sign in / Sign up

Export Citation Format

Share Document