The role of CD4+ and CD8+ T cells in the Evolution of SCW Induced Arthritis and in Oral Tolerance
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Authors
Cook, Melissa A.
Issue Date
1998
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Injection of Group A streptococcal cell wall (SCW) peptidoglycan-polysaccharide
complexes in susceptible rats induces acute inflammation in the joints followed by
chronic arthritis, producing an attractive animal model for rheumatoid arthritis.
Infiltration of neutrophils into the synovium characterizes the acute phase while
accumulation of T cells and monocytes mediates the chronic phase. In this study, we first
investigated the role of CD4+ and CD8+ T cells in the evolution of SCW-induced arthritis
by in vivo immuno-deletion of these cells. We found that neither CD4+ nor CD8+ T cells
affected acute inflammation. In contrast, both CD4 + and CD8+ T cells, at least in part,
regulated the chronic response. Unexpectedly, CD8+ T cells played a more important
role in the chronic phase because their deletion caused a dramatic increase in IL-4, an
anti-inflammatory cytokine. Importantly, oral administration of SCW is known to
suppress SCW induced arthritis in a dose dependent manner, however, the cells involved
in oral tolerance are ill defined. As our second objective, we assessed the same in vivo
immuno-deletion of CD4+ and CD8+ T cells. In orally tolerized animals, both CD4+ and
CD8+ immuno-deletion resulted in an increase in the acute response, but only a partially
resolved chronic inflammation. Immunohistochemical staining revealed that TGF-~, an
anti-inflammatory cytokine, was markedly increased in the orally tolerized gut tissue, but
not in the control animals. CD4+ and CD8+ immuno-deletion reduced the amount of
TGF-𝛽 in the gut, compared to the tolerized animals. Therefore, our results demonstrated
that both CD4+ and CD8+ T cells play an inhibitory role in acute inflammation in oral
tolerance. In chronic inflammation, however, other factors may be important in helping
CD4+ or CD8+ T cells maintain tolerance.
With honors.
With honors.
Description
vii, 31 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.