Severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) has affected all inhabited continents, and India is currently experiencing a devastating second wave of coronavirus disease‐2019 (COVID‐19). Here, we examined the duration of clearance of SARS‐CoV‐2 in respiratory samples from 207 infected cases by real‐time reverse‐transcription polymerase chain reaction (RT‐PCR). A substantial proportion of COVID‐19 positive cases with cycle threshold (Ct) values more than or equal to 31 (45.7%) were subsequently tested negative for SARS‐CoV‐2 RNA within 7 days of initial detection of the viral load. A total of 60% of all the patients with COVID‐19, irrespective of their Ct values, cleared SARS‐CoV‐2 RNA within 14 days of the initial detection. Longitudinal assessment of RT‐PCR test results in individuals requiring 15–30 days to clear SARS‐CoV‐2 RNA showed a significant reduction of the viral load in samples with high or intermediate viral loads (Ct values ≤ 25 and between 26 and 30, respectively) but the follow‐up group with low viral RNA (Ct values ≥ 31) exhibited a stable viral load. Together, these results suggest that COVID‐19 positive cases with Ct values more than or equal to 31 require reduced duration to clear SARS‐CoV‐2, and thus, a shorter isolation period for this group might be considered to facilitate adequate space in the COVID Care Centres and reduce the burden on healthcare infrastructure.

Notch signaling plays a pivotal role in cell fate decision and lineage commitment of lymphocytes. Although the role of Notch in CD4+ and CD8+ αβ T cells is well documented, there are no reports on how Notch signaling regulates effector functions of γδ T cells. γδ T cells are a minor fraction in the peripheral blood but are known to play a major role in defense against pathogens and tumors. In this study, we show that Notch receptors (mRNA and protein) are expressed in peripheral γδ T cells. Inhibition of Notch signaling by γ-secretase inhibitor inhibited the proliferation and IFN-γ secretion of γδ T cells in response to stimulation with phosphoantigens and anti-CD3 mAb. In the presence of γ-secretase inhibitor, the antitumor cytolytic ability of γδ T cells was inhibited with a decreased CD107a expression. Knockdown of Notch1 and Notch2 genes in γδ T cells using small interfering RNA inhibited their antitumor cytotoxic potential. Our study describes for the first time, to our knowledge, the role of Notch as an additional signal contributing to Ag-specific effector functions of γδ T cells.

Summary Gamma delta (γδ) T cells exhibit potent anti‐Plasmodium activity but are also implicated in the immunopathology of malaria. It is currently poorly understood how γδ T cells are affected in human suffering from Plasmodium vivax infection or in symptomless individuals living in an endemic region. We examined both the percentages and expression of markers associated with immune exhaustion in γδ T cells in individuals living in a P. vivax endemic region by flow cytometry. The percentage of γδ T cells in the blood was significantly higher both in acute P. vivax‐positive patients and in individuals from an endemic region in comparison with control uninfected adults. The frequency of the expression of the exhaustion markers‐Tim‐3, Lag‐3, CTLA‐4 and PD‐1 was higher in γδ and total T cells from P. vivax‐infected patients than in those populations from control uninfected adults. Individuals from a P. vivax endemic region showed elevated percentages of Tim‐3‐, Lag‐3‐ and CTLA‐4‐positive γδ T cells and an increased percentage of Tim‐3‐positive total T cells. The phenotypic exhaustion of these cells might be a protective mechanism preventing the immunopathology associated with activated T cells and may provide a rationale for targeted manipulation of this process in diseases such as malaria.

In hepatitis B virus (HBV) infection, the immune reaction is responsible for viral clearance and preventing their spread within the host. However, the immune system is dysfunctional in patients with chronic HBV infection, leading to an inadequate immune response against the virus. A major factor contributing to inefficient immune function is the phenomenon of immune exhaustion. Hence, understanding immune activation and exhaustion during HBV infection is important, as it would provide insight in developing immunotherapy to control chronic HBV infection. The aim of this review is to highlight the existing information on immune effector functions and immune exhaustion in response to HBV infection.

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γδ T cells recognize phosphorylated antigens and play an important role in tumor immunity. The aim of the present study was to investigate the role of Notch signaling pathway in antigen specific responses of γδ T cells. Expression of mRNA for Notch1 and Notch2 genes was predominantly observed in peripheral γδ T cells. The presence of active Notch intracellular domain in γδ T cells was confirmed by confocal microscopy and western blotting. Proliferation of γδ T cells and IFN-γ release in response to phosphoantigens was inhibited in the presence of γ-secretase inhibitor confirming involvement of Notch signal. Delta like ligands 1 and 4 activated γδ T cells while Jagged1 inhibited the γδ T cell response. Oral and breast cancer cells showed dominant expression of Jagged1 ligand which may exert inhibitory signal as a way to evade immune recognition by γδ T cells. Decreased expression of CD107a and diminished lysis of tumor targets in the presence of γ-secretase inhibitor confirmed that Notch was involved in cytotoxic effector functions of γδ T cells. Thus, our data for the first time demonstrates that Notch signal plays an indispensable role in antigen specific responses of γδ T cells. Future immunotherapeutic strategies can exploit Notch signaling in γδ T cells to achieve therapeutic benefits in cancer patients.