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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

Journal Title

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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

Committee

Citation

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