HOST defense peptides BMAP-27 and BMAP-28 down-regulate proliferation of T cells through the induction of T cell anergy
Date
2010-09-07
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
Host Defense Peptides (HDPs) are small, cationic and amphipathic molecules with inherent antimicrobial and immunomodular function. However their effects on blood-derived T cells is unknown and is the focus of this investigation. In this thesis, porcine peripheral blood mononuclear cells (PBMCs) were stimulated with bovine myeloid antimicrobial peptide (BMAP)-27, BMAP-28, Indolicidin (Indol), or HH2 in the presence and absence of Concanavalin A (ConA). It was observed that BMAP-27, BMAP-28, and Indol inhibited ConA-stimulated porcine PBMC proliferation. To ensure that the observed effect on cell proliferation was not simply due to a physical interaction between the peptide and ConA, addition of peptide and ConA was staggered. Porcine CD4+/CD8+ T cells were isolated from blood using magnetic activating cell sorting (MACS) and it was determined that BMAP-27 and BMAP-28 inhibited ConA-stimulated T cell proliferation. They did not promote T cell necrosis, but approximately 40 % of the activated T cells undergoes apoptosis in the presence of BMAP-27 and BMAP-28. The remaining 60 % of the T cells consumed very little ATP and showed an increase in expression of cytotoxic T lymphocyte antigen-4 (CTLA-4), indicating the induction of T cell anergy. The addition of exogenous IL-2 decreased the surface expression of CTLA-4 in ConA- activated CD4+ T cells and induced renewed CD4+/CD8+ T cell proliferation, an indicator that these cells underwent activation-induced anergy. Thus, we submit that BMAP-27 and BMAP-28 may play a role in returning the activated T cell population to a homeostatic state through induction of peripheral tolerance mechanisms.
Description
Keywords
host defense peptides
Citation
Degree
Master of Science (M.Sc.)
Department
School of Public Health
Program
Vaccinology and Immunotherapeutics