Shobha Sehgal
PGIMER, India
Title: TLR 9 ligand ODN 2216 binds to the effector T cells from healthy controls leading to proliferation of CD4 cells & up-regulation of cytokines
Biography
Biography: Shobha Sehgal
Abstract
Toll like receptor (TLR) engagement is primarily a function of innate immune cells yet recent reports indicate that TLR9 may be expressed on certain subsets of T lymphocytes but their precise role in T effector (Teff) cells has not been elucidated. We made a chance observation that purified Teff cells from healthy individuals consistently bind to the TLR9 ligand ODN 2216. We confirmed intracellular localization of ODN 2216 FITC as well as intracellular expression of TLR9 in Teff cells. Furthermore, ODN 2216 FITC was also co localized with the lysosomal membrane associated protein 1 (LAMP1). In the whole blood, on the other hand, 98% of monocytes showed binding to ODN 2216 FITC indicating that the monocytes compete with the lymphocytes for ligand binding. The uptake of TLR ligand culminated in cellular proliferation, up-regulation of cytokines and increased mRNA expression of TLR9 and IRF7 in T effector cells. ODN uptake by Teff cells was inhibited by an endocytosis inhibitor, promethazine, as well as by TLR9 antagonist. Our results show a direct engagement of TLR9 ligand in Teff cells giving new insight into the role of TLR9 signalling and novel mechanisms of action of TLR inhibitors.