Researchers at the Gladstone Institute of Virology and Immunology have learned how T-cell levels may be maintained in people. The study has important implications for developing treatment strategies for patients who have diseases like HIV and cancer where the immune system is destroyed and for patients whose immune system is suppressed by chemotherapy or who are undergoing a bone marrow transplant, the researchers said.
The Gladstone researchers were looking for factors that regulated the levels of T-cells. T-cells are disease fighting white blood cells derived from the thymus that are essential for a healthy immune system. Infection with HIV destroys T-cells and decreases T-cell production resulting in immunodeficiency. The researchers found that the level of interleukin (IL)-7, a cytokine that stimulates production and expansion of T-cells, increases when the level of CD4+ cells (the T-cells targeted and killed by HIV) falls in HIV-infected patients. The researchers hypothesized a "compensatory feedback loop:" HIV reduces the number of T-cells; dendritic-like cells in peripheral lymph nodes sense the loss and cause the production of IL-7; IL-7 then stimulates the thymus and other immune tissues to produce T-cells in an attempt to restore T-cells to their proper level.
The lead author on the study, which is published in the January issue of Nature Medicine, Laura Napolitano, MD, is a staff scientist in the lab of co-author Joseph M. McCune, MD, PhD, a professor of medicine and senior investigator at the UCSF-affiliated Gladstone Institute for Virology and Immunology.
"Our first step was to identify the cytokine or hormone which might stimulate the production and expansion of T-cells in response to T-cell loss. We found that IL-7 increases as CD4+ cells declined. The next step was to identify the cells that could sense the depletion of T-cells and produced IL-7 in response," said Napolitano.