Growth hormone enhances thymic function in HIV-1–infected adults

Abstract

Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1-infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4 + T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4 + T cell recovery in HIV-1-infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.

Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions

“…Therefore, an effect on pre-T cell number has to be considered, in addition to the potential direct action on thymus function. Long-term GH treatment of immunodeficient HIV-infected patients leads to increase in thymic mass, in frequency of circulating TREC within PBMC, and in the number of CD4 + T cells [15]. These findings are consistent with animal studies showing that GH is able to stimulate thymopoiesis.…”

“…These findings are consistent with animal studies showing that GH is able to stimulate thymopoiesis. Furthermore, these increases of TREC frequency and T-cell gain are correlated to an increase of plasma IGF-1 [15], arguing for a crucial role of IGF-1 in GH-mediated stimulation of thymic T-cell production. Investigation of thymopoiesis in adult GH deficiency (AGHD) has demonstrated that, after GH withdrawal, intrathymic T-cell proliferation and thymic T-cell output decreased whereas resumption of GH treatment led to an increase of thymopoiesis to a level close to the one before withdrawal of GH treatment [16].…”

“…The striking result was that CD4 count, thymus volume, plasmatic IL-7 and RTE were all significantly lower in a group of HIVinfected children with GHD versus GHD negative group [129]. Thereafter, it was shown that thymopoiesis as well as the numbers of CD4 + RTE cells were increased in middleaged AIDS patients treated with GH and antiretroviral therapy [15,130]. The conclusion is that, coupled to antiretroviral therapy and especially when a GHD is evidenced, GH could be effective to enhance the restoration of a full immune response.…”

“…The evolution of the research field has brought new insights that justify an overview update as some ancient conclusions about absence of GH receptor on human differentiating T cells, or the lack of effect of GH administration on human thymopoiesis, have been recently revisited. Finally, from the data of recent studies, it has been proposed that GH and IGF-1 could be novel therapeutic agents able to enhance thymopoiesis in immunodeficient individuals [14][15][16]. …”

Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age

“…Previous effort has focused on rejuvenating the thymus (15). Though this approach will be valuable under extreme forms of lymphocyte depletion, such as after chemotherapy or HIV infection (47), it may have little effect on age-associated contraction in diversity. Instead, our model suggests that treatment would require an intervention that targets the specific cells growing abnormally and pushing other TCR lineages toward stochastic extinction.…”