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Title: NEITHER CD28 OR B7-2 IS REQUIRED FOR GERMINAL CENTER FORMATION DURING A B7-DEPENDENT TYPE 2 IN VIVO MUCOSAL IMMUNE RESPONSE

Author
item GREENWALD, R - UNIFORMED SERVICES, MD
item NGUYEN, DIEP - UNIFORMED SERVICES, MD
item FINKLELMAN, FRED - UN CINCINNATI, OH
item LINSLEY, PETER - BRISTOL-MYER, SEATTLE, WA
item SHARPE, ARLENE - BRIGHAM & WOMENS HOSP, MA
item Urban, Joseph
item GAUSE, WILLIAM - USUHS, BETHESDA, MD

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: The interaction between a parasite and the immune system of the host that it infects can lead to resistance or susceptibility. Knowledge of how these two distinct outcomes are regulated by the host is important in the design of effective strategies to control infectious diseases of humans and livestock. The current study demonstrates that worm parasites stimulate a strong and characteristic response that leads to an effective immunity whe cells that bear particular cell surface molecules are activated. A particular pattern of molecular interaction is required in order for the complete set of host immune responses to be effectively activated. This information is relevant to researchers that are interested in producing vaccines against worm parasites for the control of the level and intensity of the infection. This observation is unique because it shows for the first time that worms induce a pattern of cell surface molecular interactions that is not the same as that required by isolated proteins that are often used to immunize against the parasite. This observation suggests that new stimulators of the immune system must accompany vaccination with isolated proteins if the response is to be effective against the worm infection.

Technical Abstract: The T-dependent immune response requires B7-ligand interactions for the development of humoral immunity and the associated germinal center (GC) reaction, which is the in vivo site of T:B cell interactions leading to the production of high affinity antibodies and memory. However, the requirements of B7-1/B7-2 and CD28/CTLA-4 for GC formation remain unclear. Few studies have examined the role of these individual molecules in the development of infectious disease. We observed that GC formation and elevated serum IgG1 levels are comparable to wild-type mice in B7-1, B7-2 and CD28-deficient mice following oral infection with Heligomosomoides polygyrus (Hp). Administration of anti-B7-1 antibody to Hp-inoculated B7- 2-/- mice or administration of CTLA-4Ig to Hp-inoculated CD28-/- mice blocks elevations in serum IgG1 levels and GC formation. Thus, there is an obligatory requirement for either B7-1 and a ligand other than CD28 can provide the required B7-dependent costimulatory signals leading to antibod secretion and GC formation during a Th2 mucosal immune response to a pathogen.