Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD40 ligand (also called CD40L, CD154, or TNFSF5) is a membrane protein expressed mainly by activated CD4+ T cells, which interacts with its receptor, CD40, on a variety of cells. The crucial importance of the CD40L-CD40 system 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 control of viral replication by inducing HIV-suppressive chemokines and supporting the production of anti-HIV antibodies and cytotoxic T cells. However, by activating antigen-presenting cells, such as dendritic cells and macrophages, CD40L can also lead to increased CD4+ T cell activation, which promotes the replication of HIV in these lymphocytes. Later, with the development of AIDS, CD40L-expressing CD4+ T cells become selectively depleted, perhaps as a result of a gp120-induced signal through CD4 that down-regulates CD40L expression. This acquired CD40L deficiency may explain the similarity 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 host immunity against HIV and prevent AIDS-defining opportunistic infections.
 ...
PMID:The emerging role of CD40 ligand in HIV infection. 1098 54

Immunostimulatory members of the tumor necrosis factor (TNF) superfamily (TNFSF) of ligands are known to be important regulators of the immune system. These trimeric molecules interact with members of the TNF receptor superfamily (TNFRSF) to stimulate immune cells. Of the TNFSF molecules, CD40 ligand (CD40L, also called CD154 or TNFSF5) is the most crucial molecule for activating antigen-presenting cells (APCs) and thereby initiating the immune response. Evidence has accrued indicating that HIV infection either selectively depletes those CD4(+) T cells that express CD40L in response to antigen or down-regulates CD40L expression by these cells. Because CD40L expression is necessary for the immune defense against HIV and opportunistic infections, an insufficiency of CD40L could contribute to the progression of AIDS. CD40L contributes to the antiviral mechanisms of the host by inducing anti-HIV beta-chemokines and activating CD8(+) T cells. However, CD40L stimulation can lead to enhanced HIV replication under certain experimental conditions, due to its immune activating properties and the need for cellular activation for high-level HIV production. On balance, it is believed that reversing the relative CD40L deficiency seen in HIV infection will be important for immune restoration in AIDS. In addition, adding CD40L to a therapeutic or preventative vaccine could lead to strengthened antiviral immunity. Because of the complexities in delivering this molecule, a number of forms of CD40L have been developed, and one form of soluble CD40L has been tested in humans. New strategies are being developed to translate the profoundly immunostimulatory effects of CD40L found in animal models to humans with HIV infection.
 ...
PMID:An expanding role for CD40L and other tumor necrosis factor superfamily ligands in HIV infection. 1242 85