IL-2 and IL-7 Determine the Homeostatic Balance between the Regulatory and Conventional CD4+ T Cell Compartments during Peripheral T Cell Reconstitution

Campion, Armelle Le; Pommier, Arnaud; Delpoux, Arnaud; Stouvenel, Laurence; Auffray, Cédric; Martin, Bruno; Lucas, Bruno

doi:10.4049/jimmunol.1103152

Cited by 31 publications

(26 citation statements)

References 58 publications

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“…This result seems contradictory to the work from Ribot et al (13) studies describing g/d T cell memory-type responses in mice after Staphylococcus aureus infection (35), in macaques following a secondary challenge with bacillus Calmette-Guerin (36), or in humans in a CMV infection context (37). When transferred into a lymphopenic environment, naive a/b T cells proliferate strongly and acquire a memory-like phenotype (20,27,38). In our study, we observed that naive-like Ly-6C 2 and Ly-6C + CD44 lo g/d T cell subsets were able to undergo lymphopenia-induced spontaneous proliferation and to convert to a memory-like phenotype (Ly-6C + CD44 hi ) while increasing their capacity to produce IFN-g, suggesting that these three g/d T cell subsets would actually correspond to various differentiation stages of a unique T cell lineage.…”

Section: Cd44contrasting

confidence: 55%

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Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

Lombès

Durand

Charvet

et al. 2015

The Journal of Immunology

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To better apprehend γ/δ T cell biological functions in the periphery, it appears crucial to identify markers highlighting the existence of distinct phenotypic and functional γ/δ T cell subsets. Interestingly, the expression of CD44 and Ly-6C subdivides murine peripheral γ/δ T cells into several subsets, with Ly-6C− CD44hi γ/δ T cells corresponding to the IL-17–producing CD27− γ/δ T cell subset exhibiting innate-like features. By comparing the other subsets to naive and memory CD8+ α/β T cells, in this study, we show that Ly-6C− or + CD44lo and Ly-6C+CD44hi γ/δ T cells greatly resemble, and behave like, their CD8+ α/β T cell counterparts. First, like memory CD8+ α/β T cells, Ly-6C+CD44hi γ/δ T cells are sparse in the thymus but largely increased in proportion in tissues. Second, similarly to naive CD8 α/β T cells, CD44lo γ/δ T cells are poorly cycling in vivo in the steady state, and their proportion declines with age in secondary lymphoid organs. Third, CD44lo γ/δ T cells undergo spontaneous proliferation and convert to a memory-like Ly-6C+CD44hi phenotype in response to lymphopenia. Finally, CD44lo γ/δ T cells have an intrinsic high plasticity as, upon appropriate stimulation, they are capable of differentiating nonetheless into Th17-like and Th1-like cells but also into fully functional Foxp3+ induced regulatory T cell–like γ/δ T cells. Thus, peripheral CD27+ γ/δ T cells, commonly considered as a functionally related T cell compartment, actually share many common features with adaptive α/β T cells, as both lineages include naive-like and memory-like lymphocytes with distinct phenotypic, functional, and homeostatic characteristics.

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Section: Cd44contrasting

confidence: 55%

“…Surface staining was performed as previously described (20,21). Briefly, cells were incubated on ice, for 15 min per step, with Abs in 5% FCS (Biochrom) and 0.1% NaN 3 (Sigma-Aldrich) PBS.…”

Section: Fluorescence Staining and Flow Cytometrymentioning

confidence: 99%

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

Lombès

Durand

Charvet

et al. 2015

The Journal of Immunology

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“…Therefore, increased availability of IL-7 may enhance peripheral expansion in response to both high-affinity and low-affinity antigens [8] and may promote alloreactivity to low-affinity minor antigens and thereby progression to aGVHD. In addition, elevated IL-7 levels may cause a functional shift within the T cell compartment, as IL-7 has minimal impact on the homoeostatic proliferation of regulatory T cells (Tregs) [33,43] that are thought to inhibit the development of aGVHD and found at reduced levels in patients with aGVHD [44,45].…”

Section: Discussionmentioning

confidence: 99%

T cell Reconstitution in Allogeneic Haematopoietic Stem Cell Transplantation: Prognostic Significance of Plasma Interleukin‐7

et al. 2014

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Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with antithymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3 + : b = À10.6 9 10 6 cells/l, P = 0.0030; CD8 + : b = À8.4 9 10 6 cells/l, P = 0.061; CD4 + : b = À2.1 9 10 6 cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.

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“…62 This observation has led to low-dose IL-2 as therapy to promote Treg proliferation in hepatitis C-associated vasculitis 63 and GVHD following stem cell transplantation. 64 IL-2 therapy for GVHD restores pStat5 signaling and proliferation of T regs without affecting T convs .…”

Section: Clinical Implications For Autoimmunity After Treatment Omentioning

confidence: 99%

Homeostatic expansion as a barrier to lymphocyte depletion strategies

Zwang

Turka²

2014

Current Opinion in Organ Transplantation

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Introduction Purpose of review Following lymphodepletion, lymphocytes repopulate the immune space both through enhanced thymopoiesis and proliferation of residual non-depleted peripheral lymphocytes. The term homeostatic proliferation (alternatively homeostatic expansion or lymphopenia-induced proliferation) refers to the latter process. Homeostatic proliferation is especially relevant to reconstitution of the lymphocyte compartment following immunodepletion therapy in transplantation. Repopulating lymphocytes can skew toward an effector memory type capable of inducing graft rejection, autoimmunity, or, in the case of allogeneic bone marrow transplantation, graft versus host disease. Here we review recent studies exploring the biologic mechanisms underlying homeostatic proliferation and explore implications for therapy in transplantation. Recent findings Two immune-depleting agents, alemtuzumab and rabbit antithymocyte globulin, have been well-characterized in their abilities to induce an effector-memory phenotype in repopulating lymphocytes. Additionally, we have gained new understandings of the mechanisms by which the cytokines Interleukin-7 (IL-7) and Interleukin-15 (IL-15) regulate this process. Recent studies have also explored the functions of non-cytokine and signaling molecules in lymphopnenia-induced proliferation. Finally, we have seen the promise and limitations of several therapeutic approaches, including recombinant IL-7 therapy, CD8+-targeted antibodies, and peri-transplant cyclophosphamide, to treat post-transplant lymphopenia and reduce the risks of immune dysregulation following homeostatic proliferation. Summary Immune dysfunction following homeostatic proliferation is a special challenge in transplantation. A deeper understanding of the underlying biology has led to a number of promising new therapies to overcome this problem.

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IL-2 and IL-7 Determine the Homeostatic Balance between the Regulatory and Conventional CD4+ T Cell Compartments during Peripheral T Cell Reconstitution

Cited by 31 publications

References 58 publications

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

T cell Reconstitution in Allogeneic Haematopoietic Stem Cell Transplantation: Prognostic Significance of Plasma Interleukin‐7

Homeostatic expansion as a barrier to lymphocyte depletion strategies

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