A small number of patients infected by HIV spontaneously control the replication of the virus, without the need for antiretroviral drugs. As a result, they do not go on to develop the disease. The ability of these rare patients, known as ‘HIV controllers’, to suppress HIV replication appears to be down to a highly effective immune system. Now, a team of scientists at the Institut Pasteur in Paris and Inserm, France’s national institute of health and medical research, have identified what it is that stimulates such an effective immune response. They believe that CD4+ T-immune cells in these patients are capable of recognising tiny quantities of the virus. This highly sensitive detection is dependent on the expression of specific T-cell receptors on the surface of the CD4+ immune cells, which target the HIV protein with high affinity. The preferential expression of these receptors appears to keep the immune system on a constant state of alert, thereby enabling the patients’ bodies to control HIV. ‘HIV controller’ patients represent less than 0.5 per cent of all HIV-infected people, the researchers led by Lisa Chakrabarti of the Institut Pasteur and Inserm, in collaboration with Olivier Lambotte from Bicêtre Hospital, noted. They are proof that in some cases the human immune system can resist the harmful effects of HIV. These patients’ bodies are able to maintain a population of CD4+ T lymphocyte cells. In patients that have gone on to develop the disease these cells are destroyed or rendered inactive by the infection. In order to arrive at their findings, researchers examined a group of patients living in France. To trigger the antiviral immune response, the CD4+ T-cells in ‘HIV controllers’ are able to produce numerous cytonkines - cell signalling molecules - in response to very low doses of HIV antigens. Scientists discovered that these highly sensitive responses were due to the expression of particular T-cell receptors (known as TCRs) on the surface of the ‘HIV controllers’ CD4+ T-cells. In contrast, these T-cell receptors were rarely found on the CD4+ T-cells of patients receiving treatment. Scientists hope in future immunotherpy treatments will be able to transfer or boost these key T-cell receptors, to help restore effective antiviral responses in patients who have gone on to develop HIV. These findings have been published in the Journal of Clinical Investigation.
