The Function of CTLA4 During the in vivo Immune Response to Infectious Disease
Abstract
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 I cells. CD28 ligation by B7 is a potent mediator of positive costimulation. In contrast B7 ligation of CTLA4 (CD1 52). a homologue of CD28, provides a critical downregulatory 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 na%ve I cells have differentiated to effector I cells. These data support a negative regulatory role for CTLA4 late in the response. Blockade of CTLA4 by in vivo administration of anti-CTLA4 antibody enhanced the polarized Th2 response to H. polygyrus, resulting in increased serum concentrations of immunoglobulins. IL-4 secretion. and T and B cell activation. Further evidence of enhanced immune response upon CTLA4 blockade was provided in another nematode model. Trichuris murts. Anti-CTLA4 antibody treatment increased serum immunoglobulin concentrations and T and B cell activation. The treatment also caused immune deviation from Th1 to Th2. as evidenced by decreased IFN gamma and increased IL-4 secretion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2000
- Accession Number
- ADA444388
Entities
People
- Velia Mitro
Organizations
- Uniformed Services University of the Health Sciences