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Publications (6)14.75 Total impact

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    ABSTRACT: Th17 cells play a crucial role in host immune response. We examined the role of Th17 cells in HIV-1 'subtype-C' infection and report that HIV-1 specific Th17 cells are induced in early infection and slow progressors but are significantly reduced at late stage of infection. There was a further decline in Th17 cells in late stage subjects with gastrointestinal infections. Additionally, we observed expanded population of IL-21 (needed for Th17 population expansion) producing CD4 T cells in early and slow progressors compared to subjects with late stage infection. A significant positive correlation existed between virus specific IL-17 and IL-21 producing CD4 T cells suggesting that HIV-1 infection induces a demand for Th17 cells. A significant negative correlation between virus specific Th17 cells and HIV-1 plasma viral load (pVL) was also observed, indicating a gradual loss of Th17 cells with HIV-1 disease progression.
    Cytokine 07/2012; 60(1):55-63. · 2.52 Impact Factor
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    ABSTRACT: CD4+CD8+ double positive T cells represent a minor peripheral blood lymphocyte population. CD4+ expression on CD8+ T cells is induced following cellular activation, and as chronic HIV-1 infection is associated with generalized immune activation, double positive T cells studies have become necessary to understand the immunopathology of human immunodeficiency virus (HIV). The frequency of double positive T cells in persons infected with HIV was studied in comparison to uninfected controls. Further, the expression of CD38, HLA-DR, and programmed death (PD)-1 on these cells were ascertained. HIV-1 specific double positive T cells were also studied for their cytokine secretory ability and phenotype. A significantly higher double positive cell population was observed in the patients with advanced HIV disease (CD4+ T cell counts below 200 cells/µl), as compared to patients with CD4+ T cell counts above 500 cells/µl. Double positive T cells from patients with symptomatic HIV disease had a significantly increased activation and exhaustion levels, compared to asymptomatic subjects and to single positive T cells from the same subjects. HIV-1 specific double positive T cells showed further increase in CD38 and PD-1 expression levels. The proportion of CD38 and PD-1 expressing total and HIV-1 specific double positive T cells correlated positively with HIV-1 plasma viremia and negatively with CD4+ T cell counts. HIV infection results in a marked increase of double positive T cell population, and this cell population shows higher level of activation and exhaustion (increased PD-1 expression) compared to the single positive CD4+ and CD8+ T cells.
    Journal of Medical Virology 06/2012; 84(6):845-56. · 2.37 Impact Factor
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    ABSTRACT: HIV infection is characterized by a perturbation in T cell homeostasis, leading to alteration in T cell subsets. In addition to alteration in differentiation, HIV infection also leads to change in T cell survival and regenerative capacity, as suggested by differential expression of CD127 and CD57. We evaluated the expression patterns of CD127 and CD57 on CD4 and CD8 effector, memory and naïve T cell subsets in HIV-infected and uninfected individuals. We characterized T cell subsets based on expression of these markers, and compared their expression pattern in HIV infected subjects and uninfected controls. We further assessed therapy generated changes in these subsets and expression of CD127 and CD57 on them. There was a generalized decrease in naïve CD4 and CD8 T cells in HIV infected subjects. These changes in T cell subset distribution were related to antigen load. CD127 expression was significantly reduced in T cells from HIV infected subject. In association to this, HIV infected subjects had higher percentage of T cell subsets expressing CD57. Increased CD57 and reduced CD127 expression correlated with plasma viraemia and CD8 T cell activation state. Incomplete restoration of T cell subset proportions was observed, despite suppression of viral replication and increase in CD4 T cell counts. Further, the improvement was more pronounced in CD127 expression. HIV infected subjects have reduced T cell regenerative capacity along with increased senescence, highlighting decreased proliferation and effector activities.
    The Indian Journal of Medical Research 12/2011; 134(6):972-81. · 2.06 Impact Factor
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    ABSTRACT: ABSTRACT: CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre) healthy participants were enrolled in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS), version 15) and Prism software version 5. The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population. The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.
    AIDS Research and Therapy 10/2011; 8:35. · 2.54 Impact Factor
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    ABSTRACT: HIV-1 infection is associated with depletion of naïve T cell subsets and skewed T cell differentiation and maturation, leading to accumulation of T cells at intermediate and end stages of differentiation. CD27 and CD28 expression have been utilized in assessing these population subsets. We characterized T cell subsets based on expression of CD45RA, CCR7, CD27, and CD28 and compared these subsets in HIV-1 infected Indian subjects and uninfected controls. HIV-1 infection was associated with an increase in effector and memory T cell subsets and a concomitant decrease in naïve T cells. HIV-1 infected subjects showed accumulation of intermediate CD8 T cell (CD27+CD28-) differentiation subsets, whereas CD4 T cells progressed to late stage differentiation (CD27-CD28-). These subsets were negatively associated with CD4 T cell counts and positively associated with plasma viremia. CD57, an immunosenescence marker, was also increased on T cell subsets from HIV-1 infected individuals. Antiretroviral therapy resulted in partial restoration of differentiation status. Persistent HIV-1 replication and chronic immune activation, along with altered cytokine secretion profile, lead to impaired T cell differentiation and maturation. Detailed understanding of factors associated with differentiation defects in HIV-1 infected Indian individuals will strongly assist in Indian HIV-1 vaccine efforts and add to our knowledge of HIV-1 subtype C pathogenesis.
    Cytometry Part B Clinical Cytometry 06/2011; 82(1):43-53. · 2.23 Impact Factor
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    BMC Infectious Diseases 12(1). · 3.03 Impact Factor