{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:51:38Z","timestamp":1792461098636,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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<jats:italic>Leishmania donovani<\/jats:italic>-infected BALB\/c mice by electrofusing dominant<jats:italic>Leishmania<\/jats:italic>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<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>T-cell depletion completely abrogated HCV-mediated immunity and the anti-KMP-11 CTL response. Interestingly, CD8<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>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.<\/jats:p>","DOI":"10.1128\/iai.00944-07","type":"journal-article","created":{"date-parts":[[2007,10,2]],"date-time":"2007-10-02T00:25:55Z","timestamp":1191284755000},"page":"5956-5966","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Hybrid Cell Vaccination Resolves<i>Leishmania donovani<\/i>Infection by Eliciting a Strong CD8<sup>+<\/sup>Cytotoxic T-Lymphocyte Response with Concomitant Suppression of Interleukin-10 (IL-10) but Not IL-4 or IL-13"],"prefix":"10.1128","volume":"75","author":[{"given":"Rajatava","family":"Basu","sequence":"first","affiliation":[{"name":"Department of Immunology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suniti","family":"Bhaumik","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun Kumar","family":"Haldar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kshudiram","family":"Naskar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tripti","family":"De","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal Kumar","family":"Dana","sequence":"additional","affiliation":[{"name":"Central Instrumentation Division, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Walden","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Charite-Universita\u0308tsmedizin Berlin, Humboldt University, D-10098 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Immunology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, WB, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.4049\/jimmunol.163.7.3890","volume":"163","year":"1999","unstructured":"Ahuja, S. S., R. L. Reddick, N. Sato, E. Montalbo, V. Kostecki, W. Zhao, M. J. Dolan, P. C. Melby, and S. K. Ahuja. 1999. Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection. J. Immunol.163:3890-3897.","journal-title":"J. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2935::AID-IMMU2935>3.0.CO;2-Q"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0347"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220813"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/513439"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.7160"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.1996"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4636"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4566"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<669::AID-IMMU669>3.0.CO;2-N"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.27"},{"key":"e_1_3_2_13_2","first-page":"205","volume":"14","year":"2001","unstructured":"Grogan, J. L., M. Mohrs, B. Harmon, D. A. Lacy, J. W. Sedat, and R. M. Locksley. 2001. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity14:205-215.","journal-title":"Immunity"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.6.1089"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.915"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2005.06.015"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116372"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.4049\/jimmunol.146.8.2763","volume":"146","year":"1991","unstructured":"Kaye, P. M., A. J. Curry, and J. M. Blackwell. 1991. Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis. J. Immunol.146:2763-2770.","journal-title":"J. Immunol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.3.1069-1073.1993"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4414"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5512-5520.2002"},{"key":"e_1_3_2_22_2","first-page":"416","volume":"96","year":"1994","unstructured":"Kurtzhals, J. A., A. S. Hey, A. Jardim, M. Kemp, K. U. Schaefer, E. O. Odera, C. B. Christensen, J. I. Githure, R. W. Olafson, T. G. Theander, et al. 1994. Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2-like response to gp63 and Th1-like response to lipophosphoglycan-associated protein in cells from cured visceral leishmaniasis patients. Clin. Exp. Immunol.96:416-421.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00125-X"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.57.3.484"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(02)80014-1"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.5559-5566.1999"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.5595-5602.2000"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.3.1058-1063.1994"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"7302","DOI":"10.4049\/jimmunol.162.12.7302","volume":"162","year":"1999","unstructured":"Mohrs, M., B. Ledermann, G. Kohler, A. Dorfmuller, A. Gessner, and F. Brombacher. 1999. Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J. Immunol.162:7302-7308.","journal-title":"J. Immunol."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.7.2.233-240.2000"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(2001010)31:10<2848::AID-IMMU2848>3.0.CO;2-T"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.4049\/jimmunol.161.8.4153","volume":"161","year":"1998","unstructured":"Murphy, M. L., S. E. Cotterell, P. M. Gorak, C. R. Engwerda, and P. M. Kaye. 1998. Blockade of CTLA-4 enhances host resistance to the intracellular pathogen, Leishmania donovani. J. Immunol.161:4153-4160.","journal-title":"J. Immunol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.8.2185-2197.2001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.4.2487-2490.2006"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.4049\/jimmunol.148.6.1858","volume":"148","year":"1992","unstructured":"Murray, H. W., K. E. Squires, C. D. Miralles, M. Y. Stoeckle, A. M. Granger, A. Granelli-Piperno, and C. Bogdan. 1992. Acquired resistance and granuloma formation in experimental visceral leishmaniasis: differential T cell and lymphokine roles in initial versus established immunity. J. Immunol.148:1858-1863.","journal-title":"J. Immunol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4433"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.12.4894-4899.1995"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(99)00108-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082305"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.6.3470"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.7064"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm933"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4804-4807.2003"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.4049\/jimmunol.140.11.3971","volume":"140","year":"1988","unstructured":"Stern, J. J., M. J. Oca, B. Y. Rubin, S. L. Anderson, and H. W. Murray. 1988. Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis. J. Immunol.140:3971-3977.","journal-title":"J. Immunol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230934"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021556"},{"key":"e_1_3_2_47_2","first-page":"951","volume":"9","year":"2002","unstructured":"Sundar, S., and M. Rai. 2002. Laboratory diagnosis of visceral leishmaniasis. Clin. Diagn. Lab. Immunol.9:951-958.","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"e_1_3_2_48_2","first-page":"394","volume":"83","year":"2005","unstructured":"Sundar, S., and H. W. Murray. 2005. Availability of miltefosine for the treatment of kala-azar in India. Bull. W. H. O.83:394-395.","journal-title":"Bull. W. H. O."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1086\/318121"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065543"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20191"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000301)85:5<618::AID-IJC4>3.0.CO;2-Z"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040172"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2005.73.871"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403688200"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01868659"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00944-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00944-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T09:02:59Z","timestamp":1684054979000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00944-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12]]},"references-count":55,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["10.1128\/IAI.00944-07"],"URL":"https:\/\/doi.org\/10.1128\/iai.00944-07","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12]]},"assertion":[{"value":"2007-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-09-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}