CD40 activation: lessons for HIV immunotherapy from malignancies?
In HIV, the immune defects seen are due not only to a decrease in T-cell numbers, but also to qualitative impairment in T-cell function as well as decreased antigen-presenting cell (APC) function. These defects in cell-mediated immunity lead to increased level of infection, contributing to inability to clear the HIV virus, and an increased incidence of tumours. One of the major defects in HIV appears to be the failure of CD4 T cells to provide CD 154 (CD40 ligand)-mediated help, which is required for APC function. In lymphomas, activation through CD40 leads to increased APC activity and induction of immune responses against tumours. Such an effect may also be useful in HIV to increase response against the virus and improve immune surveillance of tumours.
Le Dieu
Rifca
R
CRUK Medical Oncology Unit, St Bartholomew's and The London School of Medicine, Queen Mary, University of London, UK.
Gribben
John
J
D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000209:etiology* / Q000276:immunology
D019013:CD40 Antigens; D018796:Immunoconjugates; D023201:CD40 Ligand