Characterization of pre-existing and induced SARS-CoV-2-specific CD8(+) T cells
Authors: Schulien, Isabel; Kemming, Janine; Oberhardt, Valerie; Wild, Katharina; Seidel, Lea M.; Killmer, Saskia; Sagar; Daul, Franziska; Salvat Lago, Marilyn; Decker, Annegrit; Luxenburger, Hendrik; Binder, Benedikt; Bettinger, Dominik; Sogukpinar, Oezlem; Rieg, Siegbert; Panning, Marcus; Huzly, Daniela; Schwemmle, Martin; Kochs, Georg; Waller, Cornelius F.; Nieters, Alexandra; Duerschmied, Daniel; Emmerich, Florian; Mei, Henrik E.; Schulz, Axel Ronald; Llewellyn-Lacey, Sian; Price, David A.; Boettler, Tobias; Bengsch, Bertram; Thimme, Robert; Hofmann, Maike; Neumann-Haefelin, Christoph
Emerging data indicate that SARS-CoV-2-specific CD8(+) T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals(1-5). However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8(+) T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8(+) T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8(+) T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8(+) T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8(+) T cells exhibited functional characteristics comparable to influenza-specific CD8(+) T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8(+) T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection. Functionally competent memory CD8(+) T cells specific for different viral epitopes are induced by SARS-CoV-2 infection and can be detected in the absence of virus-specific antibodies.
IL-27 along with IL-28B ameliorates the pulmonary redox impairment, inflammation and immunosuppression in benzo(a)pyrene induced lung cancer bearing mice
Authors: Majumder, Debabrata; Debnath, Rahul; Maiti, Debasish
Aims: The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8 + T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue. Main method: BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysis, cell cytotoxicity assay, real-time PCR assay etc. were performed to evaluate the modulatory role of IL-27 and IL-28B. Key findings: We observed that IL-27 and IL-28B were able to suppress the expression of lung cancer-associated NFkB, COX-2, and iNOS. The expression of TNF-alpha, PCNA and some matrix remodeling enzymes were also modulated upon IL-27 and IL-28B treatment. Although the population of lung residing CD8 + T cells in tumor bearing lung tissue were unresponsive but the activity of systemic CD8 + cells was increased. Significance: Results hinted that IL-27 along with IL-28B were able to ameliorate various hallmarks ranging from angiogenesis to inflammation associated with the BaP-induced lung carcinogenesis. From this study, we propose that IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer.