Dr. Shobha Sehgal is an emeritus professor of immunopathology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She is the past president of the Indian Immunology Society and founder president of the Indian Society of Primary Immune Deficiencies. Has worked in HIV and AIDS in North India including early spread, the type of virus prevalent, spectrum and immunological characteristics of Clade C virus. She has interest in other infectious diseases like leishmaniasis tuberculosis, autoimmune diseases including SLE. She has more than 250 publications to her credit. Currently she is working in the field of ocular immunology.
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.
Olga Radinsky is a PhD student under supervision of Professor Angel Porgador, doing research at the immunology field at Ben Gurion University of Negev in Israel. As a part of PhD studying, they developed cell-based reporter system based on the expression of CD3zeta-fused FcγRs in BW cells to quantitate total and pathogen-specific antibody binding to Fcγ-Receptors. Using this system they completed analysis of sera from patients with different health conditions: Alzheimer patients, cancer patients, recurrent abortions in women, and long-recovered survivors of SUDV infection.
Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors’ sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.