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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
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High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART.

L A Ramirez1, T A Arango1, E Thompson1

  • 1Department of Pathology and.

Journal of Leukocyte Biology
|August 27, 2014
PubMed
Summary
This summary is machine-generated.

Elevated levels of IP-10 in HIV-1 patients on ART impair T cell function. Modulating IP-10 may improve immune responses to infections and vaccines in these individuals.

Keywords:
CXCL10antiretroviral therapychemokinesimmune responsesinfection

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Area of Science:

  • Immunology
  • Virology
  • Infectious Diseases

Background:

  • Individuals with Human Immunodeficiency Virus type 1 (HIV-1) on antiretroviral therapy (ART) exhibit altered immune cytokine and chemokine profiles.
  • Systemic changes in cytokines and chemokines can significantly impact immune responses.
  • Increased levels of Interferon gamma-induced protein 10 (IP-10) are observed in the serum of HIV-1 infected individuals on stable ART compared to uninfected individuals.

Purpose of the Study:

  • To investigate the effect of IP-10 on immune cell function in HIV-1 infected individuals on ART.
  • To explore the potential of IP-10 modulation as a therapeutic strategy to enhance T cell responses.

Main Methods:

  • In vitro studies exposing peripheral blood mononuclear cells (PBMCs) to IP-10.
  • Assessment of cytokine secretion (e.g., Interferon-gamma) upon stimulation with recall antigens.
  • Analysis of antigen-specific calcium signaling and MAPK38 phosphorylation.
  • Evaluation of the effect of an IP-10 neutralizing antibody (Nab) on immune responses.

Main Results:

  • Exposure to IP-10 significantly reduced the number of PBMCs capable of secreting IFN-γ and other cytokines when stimulated with recall antigens.
  • IP-10 treatment led to diminished antigen-specific calcium signaling and MAPK38 phosphorylation.
  • Treatment with an IP-10 Nab successfully enhanced cytokine secretion and proliferative responses.

Conclusions:

  • IP-10 plays a crucial role in suppressing T cell function in HIV-1 infected individuals on ART.
  • Targeting IP-10 with specific drugs or antibodies may represent a promising approach to bolster T cell immunity.
  • IP-10 modulation could potentially improve the efficacy of vaccinations and enhance control of HIV-1 infection in treated individuals.