Growth hormone enhances thymic function in HIV-1–infected adults
Laura A. Napolitano, … , Peter Bacchetti, Joseph M. McCune
Laura A. Napolitano, … , Peter Bacchetti, Joseph M. McCune
Published February 21, 2008
Citation Information: J Clin Invest. 2008;118(3):1085-1098. https://doi.org/10.1172/JCI32830.
View: Text | PDF
Research Article

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.

Authors

Laura A. Napolitano, Diane Schmidt, Michael B. Gotway, Niloufar Ameli, Erin L. Filbert, Myra M. Ng, Julie L. Clor, Lorrie Epling, Elizabeth Sinclair, Paul D. Baum, Kai Li, Marisela Lua Killian, Peter Bacchetti, Joseph M. McCune

×

Figure 4

GH treatment is associated with increases in naive T cells in HIV-1–infected adults.

Options: View larger image (or click on image) Download as PowerPoint
GH treatment is associated with increases in naive T cells in HIV-1–infe...
(A) Representative phenotypic analysis of CD4+ and CD8+ naive T cells by flow cytometry. CD11a staining was used to identify a subset of non-naive CD45RA+CD62L+CD11abright T cells and a subset of true naive CD45RA+CD62L+CD11adim T cells. Higher percentages of CD45RA+CD62L+ non-naive T cells were observed among CD8+ T cells. (B and C) Comparison of changes in the GH arm versus observational controls over the first year of the study demonstrated significant increases in the percentage (B, left) and absolute count (C, left) of NCD4 (red) and TNCD4 (orange) cells. There were no increases in the percentage (B, right) and small, nonsignificant increases in the absolute count (C, right) of NCD8 cells (blue) in the GH arm (compared with observational controls) over the first year of the study. TNCD8 (green) increased significantly over the first year of the study in the GH arm. (D) GH-associated increases (circles) in NCD4 cells were confirmed by regression analysis including GH treatment data from observational controls. (E) GH-associated increases (circles) in TNCD8 cells trended toward statistical significance in comprehensive regression analysis. Estimated changes with 95% CIs are shown. Regression analysis estimated the effects of 1 year of GH treatment compared with changes over 1 year in the absence of GH. Median values are shown in B and C. CIs and additional data are shown in Tables 2 and 3. *P < 0.05 for comparison of GH versus no GH.