Role of interleukin‐7 in bone and T‐cell homeostasis

Lee, Sun-Kyeong; Surh, Charles D.

doi:10.1111/j.0105-2896.2005.00339.x

Cited by 61 publications

(36 citation statements)

References 154 publications

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“…IL-7 is produced by non-hematopoietic stromal and epithelial cells in the thymus, bone marrow, intestine, and lymphoid tissue, 43 but also by dendritic cells 44,45 and B cells. 46 Others have found an inverse correlation between IL-7 and lymphocyte numbers post-HSCT.…”

Section: Discussionmentioning

confidence: 99%

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Melenhorst

Tian

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundAllogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri-and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation. Design and MethodsWe examined the levels of 33 cytokines in relation to peri-and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies. ResultsWe identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism. ConclusionsOur results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534

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Section: Discussionmentioning

confidence: 99%

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Melenhorst

Tian

et al. 2011

Haematologica

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“…BM contains T cell survival factors, such as IL-7 and IL-15, which are recognized to induce Ag-independent proliferation of memory T cells (25,42,43). Interestingly, we did not find differences in IL-7R␣ nor IL-15R␣ expression in BM vs PB T EM .…”

Section: Discussionmentioning

confidence: 99%

Human Bone Marrow: A Reservoir for “Enhanced Effector Memory” CD8+ T Cells with Potent Recall Function

Zhang

Dong

Lin

et al. 2006

The Journal of Immunology

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The role of human bone marrow (BM) CD8+ T cells in the immune response to viral Ags is poorly defined. We report here the identification and characterization of a functionally enhanced effector memory CD8+ T cell population (TEM) in the BM of patients undergoing total joint replacement for osteoarthritis. These BM-derived TEM differ strikingly from correlate cells in peripheral blood (PB), expressing elevated levels of CD27, HLA-DR, CD38, CD69, and unique patterns of chemokine receptors. Interestingly, while BM TEM have low levels of resting perforin and granzyme B, these molecules evidence profound up-regulation in response to TCR stimulation resulting in enhanced cytotoxic potential. Moreover, compared with the TEM subset in PB, BM CD8+ TEM cells demonstrate a more vigorous recall response to pooled viral Ags. Our results reveal that human BM serves as a repository for viral Ag-specific TEM with great therapeutic potential in vaccine development.

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“…IL-7 was first identified as a pre-B-cell growth factor and plays a role in survival and proliferation of precursor B cells [2]. T-cell homeostasis is significantly affected by IL-7 [1], which also influences overall T-cell differentiation and the conversion of effector T cells into memory T cells by facilitating T-cell survival [3,4].…”

Section: Introductionmentioning

confidence: 99%

Marked enhancement of antigen‐specific T‐cell responses by IL‐7‐fused nonlytic, but not lytic, Fc as a genetic adjuvant

et al. 2010

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IL-7 plays a crucial role in the homeostatic proliferation, differentiation and survival of T cells, as well as in the survival and proliferation of precursor B cells. Here, we demonstrated that utilizing nonlytic Fc-fused IL-7 (IL-7-Fc m ) as a genetic adjuvant significantly enhanced not only CD4 1 but also CD8 1 T-cell responses by E7 DNA immunization, in addition to improving protection against TC-1-induced tumors in comparison to IL-7 alone. Similar results were obtained in OT-1 adoptive transfer experiments with OVA DNA injection, suggesting independence from antigenic nature and experimental conditions. In particular, the increased frequency of CD8 1 T cells was mainly due to enhanced T-cell proliferation in T-cell priming, and not to decreased cellular apoptosis. Interestingly, the enhanced adjuvant effect was not seen in the co-delivery of lytic Fc-fused IL-7 (IL-7-Fc) which increases T-cell apoptosis as well as T-cell proliferation, suggesting that the T-cell proliferative effect may be neutralized by T-cell apoptosis. Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4 1 and CD8 1 T-cell responses.

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Role of interleukin‐7 in bone and T‐cell homeostasis

Cited by 61 publications

References 154 publications

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Human Bone Marrow: A Reservoir for “Enhanced Effector Memory” CD8+ T Cells with Potent Recall Function

Marked enhancement of antigen‐specific T‐cell responses by IL‐7‐fused nonlytic, but not lytic, Fc as a genetic adjuvant

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