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Potential role for interleukin-10 in the immunosuppression associated with kala azar

B J Holaday1, M M Pompeu, S Jeronimo

  • 1Department of Medicine and Microbiology/Immunology, University of California, San Francisco School of Medicine 94143.

The Journal of Clinical Investigation
|December 1, 1993
PubMed

Insights

Patients with acute kala azar exhibit suppressed immune responses. CD8+ T cells from these patients inhibit T cell proliferation and interferon-gamma release, potentially via IL-10, contributing to disease progression.

Area of Science:

  • Immunology
  • Parasitology
  • Molecular Biology

Background:

  • Acute kala azar patients display non-reactive immune assays, including T cell proliferation and interferon-gamma (IFN-γ) production.
  • Investigating immunosuppressive factors is crucial for understanding kala azar pathogenesis.

Purpose of the Study:

  • To establish and characterize T cell lines and clones from kala azar patients and endemic controls.
  • To identify immune suppressive mechanisms contributing to the non-reactive state in acute kala azar.

Main Methods:

  • Establishment of CD4+ and CD8+ T cell lines and clones from patients with acute kala azar, post-chemotherapy, and asymptomatic controls.
  • In vitro assessment of cytokine profiles (IFN-γ, IL-6, IL-10) upon leishmania antigen stimulation.
  • Analysis of T cell subset influence on peripheral blood mononuclear cell (PBMC) responses.
  • Abrogation studies using antibodies against IL-10 and IL-4.

Main Results:

  • T cell lines from acute/treated kala azar patients were CD8+ biased, unlike CD4+ biased lines from controls.
  • CD8+ T cells from acute patients suppressed lymphoproliferation and IFN-γ release while increasing IL-6 and IL-10 in PBMCs.
  • IL-10, but not IL-4, partially abrogated the inhibitory effects of CD8+ cells.
  • Elevated IL-10 release was observed in acute kala azar patients but not in asymptomatic individuals.

Conclusions:

  • CD8+ T cells play a significant role in the immunosuppression observed during acute kala azar.
  • Interleukin-10 (IL-10) production by CD8+ T cells contributes to the suppression of IFN-γ release, a key anti-leishmanial cytokine.
  • Understanding these immune dysregulations is vital for developing effective kala azar treatments.

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