HIV infection deregulates Tim-3 expression on innate cells: combination antiretroviral therapy results in partial restoration

J Acquir Immune Defic Syndr. 2013 Jun 1;63(2):161-7. doi: 10.1097/QAI.0b013e318285cf13.


Background: The Tim-3 receptor has been implicated as a negative regulator of adaptive immune responses and has been linked to T-cell dysfunction in chronic viral infections, such as HIV. Blocking Tim-3 has been proposed as a potential therapeutic intervention in HIV infection. However, a more detailed characterization of Tim-3 expression in the presence of HIV is required before such strategies can be considered.

Methods: In this study, we investigate Tim-3 expression on innate immune cell subsets in chronic HIV-infected individuals pretherapy and posttherapy.

Results: We report that, pretherapy, HIV infection is associated with elevated levels of Tim-3 on resting innate lymphocytes (NK, NKT, and γδ T cells), but not resting monocytes. In the absence of HIV infection, stimulation with an inflammatory stimulus resulted in decreased Tim-3 on monocytes and increased Tim-3 on NK, NKT, and γδ T cells. However, innate cells from HIV-infected donors were significantly less responsive to stimulation. Six months of combination antiretroviral therapy (cART) restored Tim-3 levels on resting NK cells but not NKT or γδ T cells. The responses of all subsets to inflammatory stimuli were restored to some extent with cART but only reached HIV-negative control levels in monocytes and NK cells.

Discussion: These results demonstrate that, during HIV infection, Tim-3 expression on innate cells is dysregulated and that this dysregulation is only partially restored after 6 months of cART. Our findings suggest that Tim-3 is differentially regulated on innate immune effector cells, and have direct implications for strategies designed to block Tim-3-ligand interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / genetics
  • Anti-HIV Agents / therapeutic use*
  • Antigens, Surface / biosynthesis
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD56 Antigen / biosynthesis
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Inflammation
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Count
  • Membrane Proteins / biosynthesis*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Anti-HIV Agents
  • Antigens, Surface
  • CD56 Antigen
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Proteins
  • Receptors, Antigen, T-Cell, gamma-delta