Article

Expansion of CD3/CD16/CD56 positive NKT cells in HIV/AIDS: the pilot study.

Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi.
Georgian medical news 01/2009;
Source: PubMed

ABSTRACT NKT cells are a subset of lymphocytes possessing features of NK cells and T cells; they play a key role in the formation of innate immune response. Upon stimulation, rapid production of large quantities of both T(h1) and T(h2) type cytokines permits them to bridge the innate and adaptive immune responses by activating NK cells, T cells, B cells and dendritic cells. Scientific knowledge has been collecting up to date toward the definition of the role of NKT lymphocytes in HIV/AIDS setting. This direction in HIV/AIDS immunopathogenesis is relatively new and quite concerning. The objective of this study was to investigate CD3+/CD16+/CD56+ NKT cell expansion in HIV/AIDS patients and explore its association with virologic and immunologic markers of HIV infection. Retrospective analysis of 30 HIV infected patients data, taken from the database of the laboratory of clinical immunology at the Infectious Diseases, AIDS and Clinical Immunology Research Center, was conducted. Results: there was slightly increased risk of higher plasma viral load related to lower NKT cell expansion. With regard to immunologic status, borderline significance between expansion of CD3/CD16/CD56 positive NKT cells and lower CD4 positive cell count was shown. However, study did not show strong associations of NKT cell expansion with either virologic or immunologic status, interestingly, all HIV/TB co infected patients where NKT cell positive, which underlines the possible role of TB in CD3+/CD16+/CD56+ NKT cell expansion phenomena in HIV infected individuals. We think these new findings may serve as prerequisite for future, larger scale research in this direction.

4 Bookmarks
 · 
388 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Innate CD1d-restricted natural killer T (NKT) cells are infected and lost in HIV-1-infected patients, and this could contribute to HIV-1 pathogenesis because NKT cells play an important role in directing both adaptive and innate immunity. Administration of interleukin-2 (IL-2) to HIV-1-infected patients leads to substantial and sustained CD4+ T-cell expansion, involving both naive and memory cells. We investigated whether IL-2 treatment could restore the NKT cell compartment in patients with primary HIV-1 infection. We show that IL-2 combined with effective antiretroviral therapy (ART) resulted in significant expansion of CD1d-restricted NKT cells. Expansion occurred in both the CD4- and CD4+ subsets of NKT cells, and expanded cells expressed the CD161 maturation marker while expression of the HIV coreceptor CCR5 was reduced. These data indicate that IL-2 treatment in combination with effective ART is beneficial for the restoration of innate NKT cell immunity in patients with primary HIV-1 infection.
    Blood 05/2006; 107(8):3081-3. · 9.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: V alpha 24 natural killer T (NKT) cells are innate immune cells involved in regulation of immune tolerance, autoimmunity, and tumor immunity. However, the effect of human immunodeficiency virus type 1 (HIV-1) infection on these cells is unknown. Here, we report that the V alpha 24 NKT cells can be subdivided into CD4(+) or CD4(-) subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4(+) and CD4(-) NKT cells frequently express both CXCR4 and CCR5 HIV coreceptors. We find that the numbers of NKT cells are reduced in HIV-infected subjects with uncontrolled viremia and marked CD4(+) T-cell depletion. The number of CD4(+) NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4(-) NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4(+) NKT cells relative to regular CD4(+) T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4(+) lymph node homing (CD62L(+)) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4(-) CD62L(-) phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients.
    Journal of Virology 09/2002; 76(15):7528-34. · 5.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses. Invariant NKT cells down-regulate autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines. Although defects in the (invariant) Valpha24+Vbeta11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Valpha24+Vbeta11+ NKT cells in human infectious disease. In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Valpha24+Vbeta11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load. Because a small minority of Valpha24+Vbeta11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Valpha24+Vbeta11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Valpha24+Vbeta11+ NKT cells by HIV-1. A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion. In this longitudinal study no evidence was found to support an important role of Valpha24+Vbeta11+ NKT cells in determining the rate of progression during HIV-1 infection.
    The Journal of Immunology 03/2002; 168(3):1490-5. · 5.52 Impact Factor

Full-text

View
17 Downloads
Available from
Jun 1, 2014