Tuberculosis-associated immune restoration syndrome in HIV-1-infected patients involves tuberculin-specific CD4 Th1 cells and KIR-negative gammadelta T cells

J Immunol. 2009 Sep 15;183(6):3915-23. doi: 10.4049/jimmunol.0804020.

Abstract

Tuberculosis (TB)-associated immune restoration syndrome (IRS) is a frequent event (10 to 30%) in HIV-1-infected patients receiving antiretroviral treatment and is associated with an increased number of IFN-gamma-producing tuberculin-specific cells. To further understand the immune mechanisms of TB-IRS and to identify predictive factors, we prospectively analyzed the Th1 and TCRgammadelta T cells known to be involved in mycobacterial defenses and dendritic cells at baseline and after antiretroviral and TB treatment in 24 HIV-1(+) patients, 11 with and 13 without IRS. At baseline, these two groups differed by significantly lower proportions of TCRgammadelta and Vdelta2(+) T cells displaying the inhibitory receptors CD94/NKG2 and CD158ah,b in IRS patients. The two groups did not differ in the baseline characteristics of CD8 or CD4 T cells or TLR-2 expression on monocytes or myeloid/plasmacytoid dendritic cells. During IRS, the increase in tuberculin-specific IFN-gamma-producing cells involved only highly activated effector memory multifunctional (IFN-gamma(+)TNF-alpha(+)IL-2(-)) CD4 T cells, whereas activated HLA-DR(+) CD4(+) T cells also increased during IRS. In contrast, dendritic cells decreased significantly during IRS and there were no changes in TLR-2 expression. Finally, the Vdelta2(+) T cells, mostly killer Ig-related receptor (KIR) (CD94/NKG2(-) and CD158(-)), significantly peaked during IRS but not in non-IRS patients. In conclusion, IRS is associated with an increase in the number of activated tuberculin-specific effector memory CD4 T cells and of KIR(-)Vdelta2(+) TCRgammadelta(+) T cells. Higher proportions of Vdelta2(+)TCRgammadelta(+) T cells lacking KIR expression are present as baseline and distinguish patients who will develop IRS from those who will not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Case-Control Studies
  • Cell Count
  • Dendritic Cells
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / immunology*
  • Immunophenotyping
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Antigen, T-Cell, gamma-delta*
  • Receptors, KIR*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / microbiology
  • Th1 Cells / immunology
  • Tuberculin / immunology*
  • Tuberculosis / immunology*

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, KIR
  • T-cell receptor Vdelta2, human
  • Tuberculin