Background:  Recombinant human growth hormone (rhGH) has beneficial effects on the immune system. It can affect and improve thymic function, and also act locally on peripheral blood mononuclear cells (PBMC). In HIV-1 infection thymic function is impaired, resulting in reduced production of naïve T cells, which are required to control infection. We studied the effects of rhGH in vitro and in vivo on T cell function and phenotype, during treated HIV-1 infection.

Methods:  PBMC from healthy controls and HIV-1-infected individuals were cultured with rhGH for 72 hours, at 2 pharmacological concentrations. Cells were stained at baseline and after culture to determine CD4 and CD8 T cell memory/differentiation status, activation, and apoptosis markers. Lymphocyte proliferation was assessed using the conventional tritiated thymidine incorporation assay. Results were compared to those obtained from patients enrolled on a randomized, double-blind, placebo-controlled study to receive daily rhGH therapy, where we measured the proliferation of CD4 T cells, interferon-gamma (IFN-γ) -production by CD8 T cells using enzyme-linked immunosorbent spot (ELISpot) assays, and assessed T cell receptor excision cells (TREC), and pro-viral DNA levels. The assays were carried out at baseline (before GH therapy), at 12 weeks (after GH therapy) and at 24 and 48 weeks follow-ups.

Results:  We calculated the change from baseline in expression of several markers on CD4 and CD8 T cells cultured with rhGH. After culture, fewer CD4 cells expressed CD38 (marker of activation/disease progression) and HLA-DR (marker of activation), in HIV-1⁺ patients but not in healthy controls (p = 0.008). There was a significantly larger decrease in CD8 T cells that expressed CD95 and CD57 (FasL and marker of senescence respectively) from baseline, when HIV-1⁺ patients were compared to healthy controls (p = 0.015). Memory status of T cells did not change. Daily administration of rhGH in vivo significantly increased HIV-1 specific CD4 proliferative responses and IFN-γ production by CD8 T cells. These responses declined with less frequent dosing. There was a significant enhancement of T cell maturation and proliferation, and an increase in naïve CD4 T cells (all p values <0.05). TREC levels and pro-viral DNA remained stable.

Conclusions: These data indicate that administration of rhGH has a beneficial effect on the thymus of HIV-1⁺ patients. Furthermore, the in vitro data indicate that beneficial effects of rhGH on T cells in the periphery may correlate with a reduction of activation and senescence markers.