The Function of CTLA4 During the In Vivo Immune Response to Infectious Disease
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD BETHESDA United States
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CD4 T cells play a key role in the adaptive immune response to foreign antigens. For T cells to be activated, two signals are required. The first signal is delivered through antigen recognition by the T cell receptor. A second or costimulatory, signal is also required for optimal activation of T cells. CD28 ligation by B7 is a potent mediator of positive costimulation. In contrast, 87 ligation of CTLA4 CD152, a homologue of CD28, provides a critical down regulatory signal. Recent data has suggested that CTLA4 may also share some stimulatory functions with CD28. Because costimulatory molecule interactions are critical for many immune responses, a greater understanding of CTLA4 function may promote development of immunotherapies where enhancement or inhibition of the immune response would be clinically beneficial. This research was directed at developing a greater understanding of CTLA4 function in the immune response to infectious disease. A murine model of gastrointestinal nematode infection, Heligmosomoides polygyrus, was utilized in this research to investigate the role of CTLA4 after onset of infection, once naive T cells have differentiated to effector T cells.