Masters Theses

Date of Award

8-2000

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Habib Zaghouani

Committee Members

Barry T. Rouse, Robert N. Moore

Abstract

Prior investigations from this laboratory reported that exposure of the neonatal immune system to an immunoglobulin (Ig) chimera carrying a proteolipid protein (PLP) peptide drives the adult response to a challenge with the PLP peptide towards T cell deviation in the lymph node and an IFN-y-dependent T cell energy in the spleen. In addition, such exposure protects against experimental allergic encephalomyelitis (EAE). Herein, we wished to determine whether such a biased response is intrinsic to the PLP peptide or emanates from the delivery by Ig, thus allowing a similar outcome to ensue with other myelin peptides. Accordingly, the amino acid sequence 87-99 of myelin basic protein (MBP) was expressed on the same Ig backbone, and the resulting Ig-MBP chimera was tested for induction of neonatal immunity and protection against EAE involving diverse T cell specificities. The results revealed Th2 deviated T cell responses in both lymphoid organs, and the animals resisted induction of EAE. More striking, the splenic T cells produced IL-10 in addition to IL-4, providing an environment that facilitated bystander deviation of responses to unrelated encephalitogenic determinants and promoting protection against autoimmunity involving diverse T cell specificities. Thus, exposure of the neonatal immune system to antigenic peptides in the context of a self-Ig molecule fosters the development of a broad-spectrum protective immunity emanating from organ specific regulatory functions.

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