HOST PROTECTION AND CYTOKINE PRODUCTION ARE B7-INDEPENDENT IN THE TH2 IMMUNE RESPONSE TO THE GASTROINTESTINAL NEMATODE PARASITE, NIPPOSTRONGYLUS BRASILIENSIS

Authors: LIU, QIAN - UNIF SERV UNIV; LIU, ZHUGONG - UNIF SERV UNIV; EKKENS, MELINDA - UNIF SERV UNIV; FANG, HUI - UNIF SERV UNIV; WHITMIRE, JEANNETTE - UNIF SERV UNIV; CHEN, ANDY - UNIF SERV UNIV; SHARPE, ARLENE - HARVARD UNIV; Urban, Joseph; GAUSE, WILLIAM - UNIF SERV UNIV

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2002
Publication Date: 12/5/2002
Citation: Liu, Q., Liu, Z., Ekkens, M., Fang, H., Whitmire, J., Chen, A., Sharpe, A., Urban Jr, J.F., Gause, W. 2002. Host protection and cytokine production are b7-independent in the th2 immune response to the gastrointestinal nematode parasite, nippostrongylus brasiliensis. Journal of Immunology. 169:6959-6968 (2002)

Interpretive Summary: Parasitic worms are a common infection in livestock and humans. Infections in livestock are important because of their economic impact on animal quality and feed efficiency. Infections in humans are important because they affect the vitality of the individual. There are no commercially effective vaccines against worm parasites. However, activation of immunity yto worm parasites has many advantages over the common use of drugs that ar available to cure infections. It is important to know how worms activate the immune system in order to design effective vaccination strategies. This study demonstrates that a particular set of cell surface molecules, B7-1 and B7-2, are required for activation of an immune response to long- lived parasites differently from those parasites that have brief infections in the host. The former is the case with most infections of economic and medical importance. The work opens a new area of research to find activators of B7-1 and B7-2 that might be helpful in stimulating the immun response to chronic worm infections. These studies will benefit mostly scientists involved in basic research on the immunological control of parasitic infections.

Technical Abstract: Considerable evidence has suggested that Th2 responses are dependent on B7 costimulatory molecule interactions. To further address this hypothesis, B7-1/B7-2-/- double deficient BALB/c mice were inoculated with 500 Nippostrongylus brasiliensis larvae, which trigger a Th2 host protective immune response. Surprisingly, worm expulsion and egg production was comparable at day 8 and day 14 in N. brasiliensis -inoculated BALB/c B7- 1/B7-2-/- and B7-1/B7-2+/+ mice. ELISPOT and quantitative RT-PCR analyses showed pronounced and comparable increases in IL-4 in mesenteric lymph node (MLN) at day 14 after N. brasiliensis-infection in BALB/c B7-1/B7-2-/- and B7-1/B7-2+/+ wildtype controls. Treatment with anti-CD4 mAb blocked host protection and elevations in IL-4 in N. brasiliensis-inoculated BALB/c B7- 1/B7-2-/- and B7-1/B7-2+/+ controls. Elevations in total serum IgE and antigen specific IgG1 were not observed at day 8 and day 14 after N. brasiliensis infection of BALB/c B7-1/B7-2-/- mice but were pronounced in brasiliensis-inoculated B7-1/B7-2+/+ mice. In contrast, the Th2 immune response, including cytokine production, to H. polygyrus was blocked in BALB/c B7-1/B7-2-/- mice at day 8 and day 14 after inoculation. These findings demonstrate profound differences in B7 dependence of Th2 responses to different nematode parasites. They further show that following N. brasiliensis infection, B7 costimulatory molecules are not required for the development of IL-4 producing T cells but are required for subsequent B cell antibody secretion.