Leishmania donovani infection of a susceptible host results in apoptosis of Th1-like cells: Rescue of anti-Leishmanial CMI by providing Th1-specific bystander costimulation

Gobardhan Das, Harpreet Vohra, Bhaskar Saha, Javed N. Agrewala, Gyan C. Mishra

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

A protective immune response against Leishmania donovani infection is mediated by T-helper type 1 (Th1) cells. Th1 induced cell-mediated immunity (CMI), as assessed by anti-leishmanial DTH response, is lost in a susceptible host such as BALB/c mice. Although the impaired Th1 function eventuates in unhindered parasite growth and in manifestation of the susceptible phenotype, the mechanism of down-regulation of the Th1 function is yet to be elucidated. Here, we provide evidence that the parasite down-regulates the expression of a Th1-specific costimulatory molecule, M150, on the surface of infected BALB/c mice-derived macrophages. Th cells are rendered unresponsive to anti- CD3 Ab-mediated stimulation after interaction with infected macrophages. The energized T cells produce much less IL-2, IL-4 and IFN-γ compared to those T cells which were costimulated using normal macrophages. The defect in proliferation, anti-CD3 Ab induced unresponsiveness and IFN-γ but not IL-4 production can be restored by providing bystander costimulation through M150. These results not only unfold a novel immune evasion strategy used by the parasite but also clarify the mechanism of Th1 cell debilitation during the disease. Recovery of Th1 cytokine production by bystander costimulation through M150 may help in formulating a new strategy for the elimination of intracellular parasites.

Original languageEnglish (US)
Pages (from-to)795-801
Number of pages7
JournalMICROBIOLOGY and IMMUNOLOGY
Volume42
Issue number11
DOIs
StatePublished - Jan 1 1998

Keywords

  • Costimulation
  • Leishmania
  • Th1 cells

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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