CDC National AIDS Hotline Training Bulletin #119 - January 31, 1995
Centers for Disease Control and Prevention
Patrolling immune system cells called dendritic cells may begin the HIV disease process by carrying the virus from the site of infection to the lymph nodes where other immune cells become infected, according to investigators at the National Institute of Allergy and Infectious Diseases (NIAID).
"Dendritic cells probably have particular relevance to HIV infection because they are the first immune system cells to arrive at sites of inflammation on mucous membranes, the major site of sexual transmission of HIV," says Dr. Drew Weissman, M.D., Ph.D., of the NIAID Laboratory of Immunoregulation (LIR).
Dendritic cells travel through the body and bind to foreign invaders, especially in external tissues such as the skin and the membranes of the gut, lungs, and reproductive tract. Once the cells encounter an invader, they ferry the foreign substance to lymph nodes to stimulate T cells and initiate an immune response.
Dr. Weissman and his colleagues have found that dendritic cells, taken from healthy individuals, bind HIV directly to their surfaces. In laboratory experiments these cells also bind to CD4+ T cells taken from the same individual, allowing HIV to infect the CD4+ T cells. CD4+ T cells are the critical immune system cells targeted by HIV and depleted during HIV infection.
The researchers also found that adding certain immune system signalling molecules--cytokines--enhanced or inhibited the infection of CD4+ T cells. The addition of interleukin-2, interleukin-4, interleukin-12, and interleukin-15 all significantly enhanced infection, while interleukin-10 inhibited infection. In addition, Dr. Weissman and his team found that dendritic cells induced T cells to make cytokines such as interleukin-2, which HIV needs to replicate.
"Further work on the mechanisms of HIV binding to dendritic cells and the transfer of the virus to CD4+ T cells, as well as on the cytokines that influence this process, may lead to new therapies to block or alter the initial events of HIV infection prior to significant damage to the immune system," says Dr. Weissman.
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