CD4 + T cells from HIV-1 patients with impaired Th1 effector responses to Mycobacterium tuberculosis exhibit diminished histone and nucleoprotein signatures

Academic Article

Abstract

  • © 2017 HIV + patients have an increased risk for tuberculosis disease despite clinical management with ARTs. We established a culture model of Mtb-infection in PBMCs from HIV + PPD + donors on suppressive ART (median 6.4 years) with negligible viral loads (median < 50 copies/mL) and stable CD4 + T cell counts (517 cells/mm^3). We observed that HIV + patient lymphocytes harbored a recruitment defect to Mtb-infected monocytes. To investigate these immune defects on a per cell basis, purified CD4 + T cells from HIV patients were assessed by label-free quantification protein mass spectrometry. CD4 + T cells from HIV patients displayed diminished nucleoprotein levels – notably of histone variant H2a.Z and ribonucleoprotein A1. Only within healthy donors, transcriptional regulatory histone variant H2a.Z expression was correlated to the extent of IFN-γ induction upon Mtb-infection. Our findings may explain why HIV patients exhibit prolonged immune cell dysfunction despite suppressive ART, and implicate a per cell defect of CD4 + T cells.
  • Digital Object Identifier (doi)

    Pubmed Id

  • 19289498
  • Author List

  • Seu L; Mobley JA; Goepfert PA
  • Start Page

  • 16
  • End Page

  • 23
  • Volume

  • 181