Hybrid cell vaccination resolves Leishmania donovani infection by eliciting a strong CD8(+) cytotoxic T-lymphocyte response with concomitant suppression of interleukin-10 (IL-10) but not IL-4 or IL-13
Metadata of CSIR Papers
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| Title |
Hybrid cell vaccination resolves Leishmania donovani infection by eliciting a strong CD8(+) cytotoxic T-lymphocyte response with concomitant suppression of interleukin-10 (IL-10) but not IL-4 or IL-13
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| Creator |
Basu, R
Bhaumik, S Haldar, AK Naskar, K De, T Dana, SK Walden, P Roy, S |
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| Subject |
Immunology; Infectious Diseases
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| Description |
There is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. Hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. We implemented hybrid cell vaccination therapy in Leishmania donovani-infected BALB/c mice by electrofusing dominant Leishmania antigen kinetoplastid membrane protein 11 (KMP-11)-transfected bone marrow-derived macrophages from BALB/c mice with allogeneic bone marrow-derived dendritic cells from C57BL/6 mice. Hybrid cell vaccine (HCV) cleared the splenic and hepatic parasite burden, eliciting KMP-11-specific major histocompatibility complex class I-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses. Moreover, splenic lymphocytes of HCV-treated mice not only showed the enhancement of gamma interferon but also marked an elevated expression of the Th2 cytokines interleukin-4 (IL-4) and IL-13 at both transcriptional and translational levels. On the other hand, IL-10 production from splenic T cells was markedly suppressed as a result of HCV therapy. CD8(+) T-cell depletion completely abrogated HCV-mediated immunity and the anti-KMP-11 CTL response. Interestingly, CD8(+) T-cell depletion completely abrogated HCV-induced immunity, resulting in a marked increase of IL-10 but not of IL-4 and IL-13. The present study reports the first implementation of HCV immunotherapy in an infectious disease model, establishing strong antigen-specific CTL generation as a correlate of HCV-mediated antileishmanial immunity that is reversed by in vivo CD8(+) T-cell depletion of HCV-treated mice. Our findings might be extended to drug-nonresponsive visceral leishmaniasis patients, as well as against multiple infectious diseases with pathogen-specific immunodominant antigens.
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| Publisher |
AMER SOC MICROBIOLOGYWASHINGTON1752 N ST NW, WASHINGTON, DC 20036-2904 USA
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| Date |
2011-09-20T12:12:25Z
2011-09-20T12:12:25Z 2007 |
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| Type |
Article
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| Identifier |
INFECTION AND IMMUNITY
0019-9567 http://hdl.handle.net/123456789/14267 |
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| Language |
English
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