Hossam Abdelsamed Abstract - ETD Index Page

Hossam Abdelsamed
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Doctoral Dissertation
Hossam Abdelsamed
hossams2020@hotmail.com
HP TURNS 17: T HELPER 17 CELL
RESPONSE DURING HYPERSENSITIVITY
PNEUMONITIS (HP) AND FACTORS
CONTROLLING IT
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Doctor of Philosophy
Integrated Program in Biomedical Sciences
Microbial Pathogenesis, Immunology, and
Inflammation
Elizabeth A. Fitzpatrick, Ph.D.
efitzpat@uthsc.edu
David D. Brand, Ph.D.
Fabio C. Re, Ph.D.
Graduation Date: May 2012
Susan E. Senogles, Ph.D.
Christopher M. Waters, Ph.D.
Th17, T-bet, Hypersensitivity pneumonitis
World-Wide Web Access
Abstract
Hypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by repeated
inhalation of a wide range of environmental antigens. It is characterized by alveolitis, granuloma
formation, and fibrosis. Since HP is a T cell-mediated disease, it is important to determine the
type of T cell response associated with granuloma formation and the factors that control this
response. We hypothesized that HP is associated with a predominant Th17 cell response where
both T-bet and TLRs 2 and 9 are controlling T cell response during HP. The results demonstrated
a predominant Th17 response associated with granuloma formation in the lungs of C57BL/6J

mice during granulomatous and chronic HP. We also found that T-bet KO mice exposed to
Saccharopolyspora rectivirgula (SR) were characterized by exacerbated Th17 cell response
accompanied by an increase in granuloma formation and collagen production in the lungs
compared to WT exposed mice. In an attempt to find other factors regulating Th17 development,
previous studies in our lab showed that TLR2/9 double knockout (DKO) exposed mice were
characterized by a decrease in the percentage of Th17 cells in their lungs compared to WT mice.
Consequently, we hypothesized that the decrease in Th17 response is attributed to defect in
phagocytosis, or cytokines production, or antigen presentation ability of TLR2/9 DKO antigen
presenting cells (APCs). In vitro, we found no significant difference in the phagocytosis ability
of both WT and TLR2/9 DKO BMDMs (Bone Marrow Derived Macrophages) or BMDCs (Bone
Marrow Derived Dendritic Cells). In vivo, there was no significant difference in the phagocytosis
ability of both WT and TLR2/9 DKO alveolar macrophages. Although we found that both TLRs
2 and 9 were regulating cytokine production e.g. IL-6, IL-10, and TNFα from BMDMs, we did
not find a defect in antigen presentation ability of both WT and TLR2/9 DKO splenic APCs. In
conclusion, these findings suggested the following: (1) Both granulomatous and chronic HP is
associated with a predominant Th17 response and granuloma formation; (2) T-bet plays a role in
controlling disease severity and Th17 development during HP; (3) TLR2 and 9 do not affect
APCs’ ability to phagocytose SR but they affect cytokine production; and (4) Both WT and
TLR2/9 DKO APCs are equally efficient in presenting SR antigen to T cells.
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Revised 02 May 2012