A study published today online in The Journal of Experimental Medicine has identified the population of CD4 T cells serving as the major reservoir for HIV infected cells and as the primary cell site for HIV replication and production in infected patients. The study was led by Prof. Giuseppe Pantaleo and Dr. Matthieu Perreau at the Division of Immunology and Allergy and at the Swiss Vaccine Research Institute, Lausanne University Hospital, Lausanne, Switzerland.
CD4 T cells are known to be the primary target of HIV. The CD4 T cells serving as reservoir for HIV infection and as primary site for HIV replication and production are not present in the blood and are exclusively found in the lymphoid tissues in a region called germinal centers. These CD4 T cells are called ˜T follicular helper' (Tfh) cells: they represent about 2% of the total CD4 T cells residing in the lymphoid tissues and are in close contact with B cells and help B cells to mature and produce antibodies.
“This is a major discovery for the HIV field; we have finally identified the cell population predominantly responsible for supporting active HIV replication and production,” says Prof. Pantaleo. “We have also provided evidence that the Tfh cells are likely to be responsible for residual virus replication in patients effectively treated with antiretroviral therapy.”
“HIV-infected Tfh cells hide themselves within the germinal centers where they are difficult to be reached by HIV-specific cytotoxic CD8 T cells, which generally are poorly present in germinal centers,” says Dr. Perreau.“Therefore, germinal centers represent a sanctuary for HIV replication in Tfh cells.”
“The identification of the major HIV CD4 T cell reservoir will be instrumental in developing therapeutic strategies to selectively target HIV infected Tfh cells,” says Prof. Pantaleo. “The elimination of HIV infected Tfh cells will represent a critical therapeutic strategy to achieve HIV functional cure, i.e. control of HIV replication in the absence of antiretroviral therapy, and potentially HIV eradication.”
T cells: Small lymphocytes that play a major role in cellular immunity. T cells mature in the thymus and have the ability to recognize specific antigens through the receptors expressed at their cell surface. They identify and eliminate incoming microbes such as bacteria and viruses.
CD4 T cells: are a sub-group of small lymphocytes. CD4 T cells in the blood represent 50-60% of human T cells. The CD4 molecule serves as the primary receptor for HIV. HIV causes depletion of CD4 T cells. The depletion of CD4 T cells is associated with increased susceptibility to infection with other infectious agents in the advanced stages of HIV disease.
CD8 T cells: CD8 T cells recognize viral antigens on the surface of HIV-infected cells and are capable of killing virus infected cells.
Reservoir: cell type or anatomical site, where a replication-competent form of HIV can accumulate and persist stably.
About Lausanne University Hospital
The Centre hospitalier universitaire vaudois (CHUV) is one of the five Swiss University Hospitals. Through its collaboration with the Faculty of Biology and Medicine of the University of Lausanne, the CHUV plays a leading role in Europe in medical care, research and education.
About the Swiss Vaccine Research Institute (SVRI)
The SVRI is a partnership of five research institutes in Switzerland. The SVRI was created in 2007 in Lausanne and is supported by the Swiss Secretariat of Education and Research. Its primary objective is to develop effective preventive vaccine strategies and therapeutic vaccine interventions for infectious diseases and for cancer. SVRI plays an instrumental role in linking basic research to translational research. SVRI's research program targets primarily HIV/AIDS, malaria, tuberculosis, as well as the emerging influenza pandemic threat. SVRI benefits also from ongoing efforts in the area of cancer vaccine research. The SVRI hosting house is the Lausanne University Hospital (Lausanne, Switzerland).