Regardless of the initial route of infection, CD4 cells in the gut-associated lymphoid tissue (GALT) become are targeted in the first few days after HIV enters into the body. There is massive and rapid depletion of CCR5+CD4+ cells in the GALT and physical disruption of the mucosal barrier. This leads to a ‘leaky’ gut that allows passage of gut bacteria, and bacterial products, into the systemic circulation. This causes a state of generalized immune activation characterized by B and T cell activation and elevated levels of proinflammatory cytokines and chemokines which lead to decrease in CD4 cells due to either a cytopathic effect or through immune activation.
HIV infection leads to low levels of CD4+ T cells through three main mechanisms :
- Direct viral killing of infected cells
- Increased rates of apoptosis in infected cells
- Killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells.
This leads to immunosenescence, because the alterations in immune function occur that parallel natural ageing. In other words, the immune system
of people infected with HIV ages much more quickly than usual.