The emerging role of CD40 ligand in HIV infection

CD40 ligand (also called CD40L, CD154, or TNFSF5) is a membrane protein exp ressed mainly by activated CD4(+) T cells, which interacts with its recepto r, CD40, on a variety of cells. The crucial importance of the CDL40L-CD40 s ystem for many immune responses has been extensively described. This review focuses on the multiple roles that this system may play in HIV infection. In early HIV infection, CD40L expression contributes to the immunological c ontrol of viral replication by inducing HIV-suppressive chemokines and supp orting the production of anti-HIV antibodies and cytotoxic T cells. However , by activating antigen-presenting cells, such as dendritic cells and macro phages, CD40L can also lead to increased CD4(+) T cell activation, which pr omotes the replication of HIV in these lymphocytes. Later, with the develop ment of AIDS, CD40L-expressing CD4(+) T cells become selectively depleted, perhaps as a result of a gp120-induced signal through CD4 that downregulate s CD40L expression. This acquired CD40L deficiency may explain the similari ty between the types of opportunistic infections that occur in AIDS and in congenital CD40L deficiency. Vaccines or other strategies that promote the growth of CD4(+) T cells capable of expressing CD40L may help to sustain ho st immunity against HIV and prevent AIDS-defining opportunistic infections.