Interleukin-7 mediates T-cell homeostasis and increases HIV-1 replication

Interleukin-7 (IL-7) produced in response to T-cell depletion facilitates T-cell production but fosters HIV-1 disease progression, according to a report in the January issue of Nature Medicine. Previous observations suggest that T-cell loss triggers a compensatory feedback mechanism that increases T-cell production, the authors explain. They hypothesized that increased production of a cytokine might be involved in this process.

Dr. Joseph M. McCune from the Gladstone Institute of Virology and Immunology in San Francisco and colleagues investigated the role of IL-7 in T-cell homeostasis and HIV-1 disease progression in 187 HIV-1-seropositive adults. IL-7 levels were strongly negatively correlated with both total CD4+ T cell-count and naive CD4+ T-cell count, the authors report. No other cytokines or hormones studied showed similar correlations.

Lymphocyte-depleted peripheral lymph nodes showed distinct IL-7 staining in cells of dendritic-cell or macrophage lineage, the report indicates, and IL-7 production was significantly higher in depleted tissue than in hyperplastic tissues. “We propose that these cells may increase production of IL-7 after `sensing’ T-lymphocyte depletion and that this occurs as part of a homeostatic response to T-cell depletion,” the scientists suggest. Increased IL-7 levels were also associated with higher HIV-1 load, the researchers note, regardless of whether patients were receiving antiretroviral therapy. This relationship held for all disease stages.

In multivariate analyses, lower CD4+ T-cell counts and higher plasma viral RNA were the only factors independently associated with elevated IL-7 levels, the investigators report. “The implications of our findings are that higher circulating levels of IL-7 in patients infected with HIV may not only stimulate the production and expansion of T cells but also the replication of HIV,” lead author Dr. Laura Napolitano commented. “Paradoxically, a physiologic feedback loop involving IL-7 could not only drive T lymphopoiesis but also accelerate HIV-mediated T cell loss.”

“IL-7 might someday be useful (without the detriment of viral replication) to enhance T lymphopoiesis in settings where the immune system has been destroyed by means other than HIV, such as chemotherapy or bone marrow transplantation, Dr. Napolitano continued. “However, it is unlikely that IL-7 will be used for clinical purposes in the near future. Much more investigation is required before IL-7 could be considered suitable for human administration.”

“Our hope is that this work will stimulate further investigation and discovery in the area of T cell homeostasis, and that this information will be useful for the development of treatments for individuals with immunodeficiency.”