A5048211558- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Autophagy in Disease and Therapy
- Developmental Biology and Gene Regulation
- interferon and immune responses
- Phagocytosis and Immune Regulation
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Chronic Lymphocytic Leukemia Research
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer-related Molecular Pathways
- Reproductive System and Pregnancy
- COVID-19 Clinical Research Studies
Institute for Stem Cell Biology and Regenerative Medicine
2016-2025
National Centre for Biological Sciences
2004-2017
Jawaharlal Nehru University
1988-2015
Tata Institute of Fundamental Research
2000-2015
Boston Children's Hospital
2010
Harvard University
2010
National Institutes of Health
1993-1998
National Cancer Institute
1993-1998
Immungenetics (Germany)
1998
Center for Biologics Evaluation and Research
1997
The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state Maharashtra late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) B.1.1.7 (Alpha)
Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity >50% by 2021. During April 2021, city became overwhelmed COVID-19 cases fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains growth advantage Delta through combination increased transmissibility reduced sensitivity to immune responses generated against earlier variants...
The Notch family of transmembrane receptors have been implicated in a variety cellular decisions different cell types. Here we investigate the mechanism underlying Notch-1-mediated anti-apoptotic function T cells using model lines as experimental system. Ectopic expression intracellular domain Notch-1/activated (AcN1) increases proteins inhibitors apoptosis (IAP) family, Bcl-2 and FLICE-like inhibitor protein (FLIP) inhibits death triggered by multiple stimuli that activate intrinsic or...
Experimental data suggest that negative selection of thymocytes can occur as a result supraoptimal antigenic stimulation. It is unknown, however, whether such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show effector cytotoxic lymphocytes (CTL) susceptible to proliferative inhibition by high dose peptide antigen, leading apoptotic death mediated TNF-alpha release. Such not reflected the cytolytic potential CTL, since concentrations antigen inhibitory for proliferation...
In vitro T-cell receptor-induced programmed cell death in both activated T cells from human immunodeficiency virus-seronegative (HIV-) donors and resting HIV+ was substantially influenced by cytokines. Addition of exogenous recombinant "type 1" lymphokines interferon gamma interleukin 2 (IL-2), as well the macrophage-produced IL-12, which favor cell-mediated responses, blocks systems T-lymphocyte death. contrast, 2" IL-4 IL-10, antibody either had no effect or enhanced these A role for...
The hypothesis that cytoplasmic proteases play a functional role in programmed cell death was tested by examining the effect of protease inhibitors on T receptor-mediated 2B4 murine hybridoma and activated cells. cysteine trans-epoxysuccininyl-L-leucylamido-(4-guanidino) butane (E-64) leupeptin, calpain selective inhibitor acetyl-leucyl-leucyl-normethional, serine diisopropyl fluorophosphate phenylmethylsulfonyl fluoride, all showed dose-dependent blocking response triggered receptor complex...
Two cell permeable peptide fluoromethyl ketone inhibitors of Interleukin-1 beta converting enzyme (ICE) family proteases were tested as apoptotic death T lymphocytes at various stages differentiation. The CPP-32-like protease activity in lysates was blocked by both the ICE inhibitor Cbz-Val-Ala-Asp(OMe)-fluoromethyl (ZVAD-FMK) well its truncated analog Boc-Asp(OMe)-fluoromethyl (BD-FMK), which failed to block ICE. In vitro murine thymocytes triggered independent agents dexamethasone,...
Abstract In vitro activation of PBLs from HIV+ individuals resulted in programmed cell death (PCD) within 2 days 58 95 blood donors, contrast to only two 30 control HIV- donors. CD4+ and CD8+ T cells donors died under these conditions, showed apoptotic nuclear morphology DNA fragmentation. To test the hypothesis that this shares a common biochemical pathway with induced by TCR cross-linking normal dividing cells, inhibitors calcium-activated cysteine protease calpain were tested for their...
Survival of differentiated cells is one several processes regulated by Notch activity, although the general principles underlying this function remain to be characterized. Here, we probe mechanism Notch-mediated survival, building on emerging evidence that apoptotic responses coordinated specialized intermediates converge mitochondria, identifying a core event in death pathways. The Bcl-2 family protein Bax such intermediate, which unifying response diverse stimuli nucleates multiprotein...
Abstract Recombinant TNF and lymphotoxin trigger the apoptotic death of normal mouse human T lymphocyte blasts in vitro. This cytotoxic effect does not involve Fas pathway differs from TNF-triggered tumor cells several respects: 1) It is a slower process, requiring 2 to 3 days; 2) it blocked, rather than enhanced, by cycloheximide; 3) based on agonistic anti-TNF receptor Abs, involves synergistic both 55-kDa TNFR1 75-kDa TNFR2, as opposed dominance for cytotoxicity. The TNF-induced potently...
Negative selection is the process by which developing lymphocyte receptor repertoire rids itself of autoreactive specificities. One mechanism negative in T cells induction apoptosis immature CD4+CD8+ (DP) thymocytes, referred to as clonal deletion. Clonal deletion necessarily cell (TCR) specific, but TCR signals alone are not lethal purified DP thymocytes. Here, we identify two distinct mechanisms TCR-specific death thymocytes can be induced. requires simultaneous and costimulatory initiated...
The progeny of T lymphocytes responding to immunization mostly die rapidly, leaving a few long-lived survivors functioning as immune memory. Thus, control this choice death versus survival is critical for There are indications that reactive radicals may be involved in pathway. We now show that, mice lacking inducible nitric oxide synthase (iNOS), higher frequencies both CD4 and CD8 memory cells persist response immunization, even when iNOS+/+ APCs used immunization. Postactivation cell by...
It is well established that target cell lysis by MHC class I-restricted CD8+ T cells an important defense mechanism during infections with intracellular pathogens or against tumor targets. On the other hand, little known about physiologic role and mechanisms of cytotoxicity CD4+ II-restricted cells. We have recently demonstrated human autoreactive specific for one candidate autoantigen multiple sclerosis, myelin basic protein, can mediate cytotoxicity. In present report, we analyze cytolytic...
The nucleus of a living cell is constantly undergoing changes in shape and size as result various mechanical forces physiology. These correlate with alterations gene expression, however it unclear whether nuclear deformation alone sufficient to elicit these alterations. We used T-cell activation model system test the coupling between (elongation) expression. Naïve surrogate antigens resulted actin dependent elongation. This was accompanied Erk NF-κB signaling induce CD69 Importantly,...
Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes non-nuclear signaling to activate autophagy, a conserved cellular response nutrient stress, regulating murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction autophagy required ligand-dependent, intracellular domain (NIC) activity, which controlled mitochondrial organization activated Tregs. Consistently, NIC...
Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high burden can result in deletion antigen-specific CTLs. We previously reported a potential mechanism for this deletion: tumor necrosis factor (TNF)-alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide-major histocompatibility complex. Here, we show that although death is mediated by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose dependence production nor...
Abstract Since the CTL secreted granule protease granzyme B can activate multiple target caspases, it has been proposed that this pathway is responsible for CTL-induced cytolysis of Fas-negative targets. However, lysis via exocytosis completely resistant to caspase inhibitors. To test possibility granzymes trigger a postcaspase cytoplasmic apoptotic leading lysis, we have examined dependence several changes associated with death. Rapid prelytic phosphatidylserine externalization was induced...
Objective To characterize the mechanism of in vitro antigen-induced apoptotic T-cell death peripheral blood mononuclear cells (PBMC) HIV-1-infected individuals. Design and methods PBMC from uninfected individuals were unstimulated or stimulated with HIV-1 envelope synthetic peptides (Env) influenza A virus to determine extent antigen-stimulated death, whether this was limited CD4+ subset, effects cytokines on death. Death assessed by nuclear morphology after 7 days culture fluorescence...
The small subunit of calpain, a calcium-dependent cysteine protease, was found to interact with the cytoplasmic domain common cytokine receptor gamma chain (gammac) in yeast two-hybrid interaction trap assay. This functional as demonstrated by ability calpain cleave vitro-translated wild-type gammac, but not gammac containing mutation PEST (proline, glutamate, serine, and threonine) sequence its domain, well endogenous mediate cleavage fashion. In T cell receptor-stimulated murine...
Cellular dependence on growth factors for survival is developmentally programmed and continues in adult metazoans. Antigen-activated T cell apoptosis the waning phase of immune response thought to be triggered by depletion cytokines from microenvironment. resulting cytokine deprivation mediated reactive oxygen species (ROS), but their source position apoptotic cascade poorly understood. RNA interference approaches implicated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase...