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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
Author(s) -
Das Gobardhan,
Vohra Harpreet,
Saha Bhaskar,
Agrewala Javed N.,
Mishra Gyan C.
Publication year - 1998
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1998.tb02354.x
Subject(s) - biology , bystander effect , leishmania donovani , immune system , immunology , leishmania , intracellular parasite , microbiology and biotechnology , cytokine , t cell , immunity , parasite hosting , leishmaniasis , visceral leishmaniasis , world wide web , computer science
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 downregulates 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 anergized 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.