Accession Number:

ADA434766

Title:

The Role of Costimulatory Molecules in the Development of Memory and Effector T Helper 2 Cells During an in vivo Immune Response to the Murine Gastrointestinal Parasite Heligmosomoides polygyrus

Descriptive Note:

Doctoral thesis

Corporate Author:

UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD F EDWARD HEBERT SCHOOL OF MEDICINE

Personal Author(s):

Report Date:

2002-09-24

Pagination or Media Count:

72.0

Abstract:

Previous studies have demonstrated the importance of costimulatory interactions for effector CD4 T helper Th cell development during the primary immune response. However, the role of costimulatory molecules in memory CD4 T cell differentiation is not well understood. One model used to study the Th immune response involves oral infection of mice with the gastrointestinal nematode parasite Heligmosomoides polygyrus. Although the primary immune response to H. polygyrus is a chronic infection, challenge immunization triggers a T-dependent memory response that impairs adult worm maturation. In the studies presented herein, the effects of costimulatory molecule blockade on T helper effector cell function during the memory response were examined. Effector T cell development was inhibited during the primary response to H. polygyrus in B7-1B7-2-- mice however, memory Th cells developed that produced IL-4 and mediated effective reductions in adult worm egg production, but did not provide effective Ag-specific B cell help or support increased germinal center GC formation. Parallel studies in H. polygyrus-challenged CD28-- mice demonstrated similar IL-4 elevations and decreases in adult worm egg production. However, Ag-specific Ab responses and increased GC formation were significantly restored in H. polygyrusinoculated CD28-- mice. Although elevations in serum IgG1 and GC formation were intact in H. polygyrus-challenged OX40L-- mice, elevations in IL-4 and serum IgE were partially inhibited, and associated with decreased worm expulsion and increased egg production. To further examine the role of OX40L in Ag-specific CD4 T cell IL-4 production following priming, adoptively transferred OVA-specific DO11.10 T cells were analyzed in the context of the H. polygyrus response. Following immunization with OVA plus H. polygyrus, Ag-specific T cell expansion, celThese studies extt

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE