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Title: DIFFERENTIAL B7-2 DEPENDENT REGULATION OF THE CHRONIC TH2 IMMUNE RESPONSE DURING INFECTIOUS DISEASE

Author
item GREENWALD, R - USUSH, BETHESDA
item Urban, Joseph
item CHEN, S - USUSH, BETHESDA
item NGUYEN, D - USUSH, BETHESDA
item FANG, H - USUSH, BETHSDA
item FINKELMAN, F - UNIV OF CINCINNATI
item SHARP, A - HARVARD
item GAUSE, W - USUSH, BETHESDA

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: Parasitic worms induce negative economic impact on livestock by interfering with feed efficiency or by increasing disease and mortality. The natural immunity that is evoked during the infection may often be responsible for the severity of the disease response. Thus, an unregulated immune response can be as deleterious to the animal as the infection itself. An understanding of how the immune response can be regulated to induce protective immunity without the consequences of tissue destruction would be helpful in designing therapeutic and prophylactic vaccines. The current study shows that molecules on the surface of regulatory lymphocyte populations can determine which components of an immune response are elevated as opposed to a general activation of many immune effector mechanisms. Inhibitors of these co-stimulatory molecules can direct immunity to only specific components that can have both positive and negative consequences on the host. The impact of this study will be to help scientists develop useful co- stimulatory molecule antagonists that can be combined with specific products from the infecting organisms to direct an appropriate, yet efficient, immunity to the infection.

Technical Abstract: T cells require CD28/CTLA-4 costimulatory molecule interactions in addition to antigen-specific signals through the T cell receptor for in vivo Th cell effector function. Some studies have suggested that the ligands for these molecules may differentially influence T cell effector cell function with B7-2 favoring Th2 response and B7-1 a Th1 response, while other studies have suggested that theses molecules may be redundant. The recent development of B7-2 deficient mice permits the direct analysis of the requirement of B7-2 during a Th2 immune response to an infectious pathogen. We have examined in B7-2 deficient mice T cell effector function and the associated Th2 immune response following infection with Heligmosomoides polygyrus, a natural murine parasitic nematode. Elevations in cytokine gene expression protein secretion were pronounced and comparable in inoculated B7-2-/- and B7-2+/+ mice at early stages of the chronic response. However, at later stage, elevations in T cell cytokine expression were markedly inhibited in H. polygyrus-inoculated B7-2-/- mice. Furthermore, increases in serum IgE were also inhibited in B7-2-/- mice, although serum IgG1 elevations and germinal center formation remained comparable between inoculated B7-2-/- and B7-2+/+ mice. These findings suggest that certain T cell dependent parameters of the Th2 response require B7-2 interactions while others do not.