Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production, published 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.”

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