Lymphocyte production capacity in HIV: links to immune activation & immune reconstitution on ART

A number of studies have documented that the body’s machinery for producing new immune system cells is impaired by HIV infection. In a new paper in the journal Blood, Delphine Sauce and colleagues delve into the issue further by analyzing circulating CD34+ hematopoietic progenitor cells (HPC) in over one hundred HIV positive individuals at various stages of disease, compared to both age-matched and elderly (75-96 years old) uninfected controls. [1]

The research reveals significant correlations between the number of HPC and multiple types of immune cells including CD4 T cells, CD8 T cells, B cells, natural killer cells and neutrophils (the strongest correlation being between circulating HPC and CD4 T cells). The number of HPC is found to decline over the course of HIV disease progression such that middle-aged HIV-positive individuals with CD4 T cell counts less than 200 had similar levels of circulating HPCs to the elderly uninfected controls.

Additional analyses show that markers of immune activation such as CD38 expression on CD8 T cells are inversely associated with HPCs; the higher the levels of immune activation, the lower the HPC counts. The researchers demonstrate that among elite controllers with declining CD4 T counts, HPC numbers and functional capacity are diminished despite persistently low viral load, consistent with the link between immune activation and CD4 T cell loss that has been reported in this population. HIV-positive individuals with poor CD4 T cell recovery despite antiretroviral therapy (ART) also show reduced HPC numbers and functional capacity compared to individuals with better immune reconstitution.

The study authors conclude that preservation of lymphocyte production capacity (lymphopoiesis) is important for preventing HIV disease progression and that strategies for enhancing lymphopoiesis should be evaluated in the setting of poor CD4 T cell recovery on ART. One approach that is currently under evaluation in a clinical trial for people on ART with CD4 T cell counts less than 250 is TXA127 (angiotensin 1-7), a drug formulation of a naturally occurring substance that may stimulate production of HPCs. [2]