Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone

Napolitano, Laura A.; Lo, Joan C.; Gotway, Michael B.; Mulligan, Kathleen; Barbour, Jason D.; Schmidt, David J.; Grant, Robert M.; Halvorsen, Robert A.; Schambelan, Morris; McCune, Joseph M.

doi:10.1097/00002030-200205240-00003

Cited by 143 publications

(104 citation statements)

References 27 publications

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“…Similar morphological events occur in mammals during age-related thymic involution, namely the expansion of the perivascular space (Gameiro et al 2010). Infection by human immunodeficiency virus (HIV) is followed by thymic involution and histological disintegration of the cortico-medullary border (Napolitano et al 2002). Similar experimental observations have been made after parasitic infection (Brito et al 2003;Gameiro et al 2010;Pérez et al 2012) and malnutrition (Savino et al 2007).…”

Section: Discussionmentioning

confidence: 63%

A novel aspect of the structure of the avian thymic medulla

et al. 2014

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We provide evidence for the compartmentalization of the avian thymic medulla and identify the avian thymic dendritic cell. The thymic anlage develops from an epithelial cord of the branchial endoderm. Branches of the cord are separated by primary septae of neural crest origin. The dilation of the primary septae produces the keratin-negative area (KNA) of the thymic medulla and fills the gaps of the keratin-positive network (KPN). Morphometric analysis indicates that the KNA takes up about half of the volume of the thymic medulla, which has reticular connective tissue, like peripheral lymphoid organs. The KNA receives blood vessels and in addition to pericytes, the myoid cells of striated muscle structure occupy this area. The myoid cells are of branchial arch or prechordal plate origin providing indirect evidence for the neural crest origin of the KNA. The marginal epithelial cells of the KPN co-express keratin and vimentin intermediate filaments, which indicate their functional peculiarity. The basal lamina of the primary septum is discontinuous on the surface of the KPN providing histological evidence for the loss of the blood-thymus barrier in the medulla. In the center of the KNA, the dendritic cells lie in close association with blood vessels, whereas the B-cells accumulate along the KPN. The organization of the KPN and KNA increases the "surface" of the so-called cortico-medullary border, thereby contributing to the efficacy of central tolerance.

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Section: Discussionmentioning

confidence: 63%

A novel aspect of the structure of the avian thymic medulla

et al. 2014

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“…There is growing interest in the clinical application of potential immunomodulators such as IL-7 to enhance T cell production and survival in the setting of human immunodeficiency (11,20,47,48). In this report, we have characterized the specific survival signals furnished by IL-7 to various thymocyte subpopulations and have examined the impact of IL-7 treatment on thymocyte survival and on viral replication in the HIV-infected human thymus.…”

Section: Discussionmentioning

confidence: 99%

Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

Napolitano

Stoddart

Hanley

et al. 2003

The Journal of Immunology

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IL-7 is a critical component of thymopoiesis in animals and has recently been shown to play an important role in T cell homeostasis. Although there is increasing interest in the use of IL-7 for the treatment of lymphopenia caused by the HIV type 1, evidence that IL-7 may accelerate HIV replication has raised concerns regarding its use in this setting. We sought to identify the effects of IL-7 on human thymocyte survival and to determine the impact of IL-7 administration on in vivo HIV infection of the human thymus. Using in vitro analysis, we show that IL-7 provides potent anti-apoptotic and proliferative signals to early thymocyte progenitors. Analysis of CD34+ subpopulations demonstrates that surface IL-7 receptor is expressed on most CD34highCD5+CD1a− thymocytes and that this subpopulation appears to be one of the earliest maturation stages responsive to the effects of IL-7. Thus, IL-7 provides survival signals to human thymocytes before surface expression of CD1a. CD4+CD8+ thymocytes are relatively unresponsive to IL-7, although IL-7 protects these cells from dexamethasone-induced apoptosis. IL-7 has a predominantly proliferative effect on mature CD4+CD3+CD8− and CD8+CD3+CD4− thymocytes. In contrast to the in vitro findings, we observe that in vivo administration of IL-7 to SCID-hu Thy/Liv mice does not appear to enhance thymocyte survival nor does it appear to accelerate HIV infection. Given the growing interest in the use of IL-7 for the treatment of human immunodeficiency, these findings support additional investigation into its in vivo effects on thymopoiesis and HIV infection.

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“…Other approaches under study to modulate thymic function include the administration of growth hormone or its analogs, 33 as well as inhibitors of sex steroids, which appear to diminish thymic function as evidenced by thymic rebound following castration of laboratory animals. 34 …”

Section: Potential Strategies To Enhance Immune Reconstitutionmentioning

confidence: 99%

Immune reconstitution following hematopoietic progenitor cell transplantation: challenges for the future

Fry

Mackall

2005

Bone Marrow Transplant

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Summary:Successful hematopoietic progenitor cell transplantation requires rapid and complete transfer of the donor hematopoietic and immune systems to the host. Whereas the uncontrolled transfer of a nontolerant donor immune system results in GVHD in many cases, strategies which diminish GVHD also diminish immune reconstitution. Thus, the reliable, rapid and safe transfer of immunity from donor to host remains a major challenge for the field. Advances in the understanding of the biology of immune reconstitution have elucidated that thymic-dependent immune reconstitution can restore global immunity, but is especially vulnerable to toxicities associated with transplant. Alternatively, homeostatic peripheral expansion can be exploited for targeted immunity toward pathogens and tumors, but is difficult to manipulate without exacerbating GVHD risk. New translatable strategies are needed to safely augment one or both of these pathways in the setting of allogeneic hematopoietic progenitor cell transplantation. Bone Marrow Transplantation (2005) 35, S53-S57.

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Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone

Abstract: GH has significant effects on the human immune system, including the reversal of thymic atrophy in HIV-1-infected adults. De-novo T cell production may thus be inducible in immunodeficient adults.

Cited by 143 publications

References 27 publications

A novel aspect of the structure of the avian thymic medulla

A novel aspect of the structure of the avian thymic medulla

Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice

Immune reconstitution following hematopoietic progenitor cell transplantation: challenges for the future

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