Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection

Bunn, Patrick T., Stanley, Amanda C., de Labastida Rivera, Fabian, Mulherin, Alexander, Sheel, Meru, Alexander, Clare E., Faleiro, Rebecca J., Amante, Fiona H., De Oca, Marcela Montes, Best, Shannon E., James, Kylie R., Kaye, Paul M., Haque, Ashraful and Engwerda, Christian R. (2014) Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection. Journal of Immunology, 192 8: 3709-3718. doi:10.4049/jimmunol.1300768


Author Bunn, Patrick T.
Stanley, Amanda C.
de Labastida Rivera, Fabian
Mulherin, Alexander
Sheel, Meru
Alexander, Clare E.
Faleiro, Rebecca J.
Amante, Fiona H.
De Oca, Marcela Montes
Best, Shannon E.
James, Kylie R.
Kaye, Paul M.
Haque, Ashraful
Engwerda, Christian R.
Title Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection
Formatted title
Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
0022-1767
Publication date 2014-04-15
Year available 2014
Sub-type Article (original research)
DOI 10.4049/jimmunol.1300768
Open Access Status DOI
Volume 192
Issue 8
Start page 3709
End page 3718
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2015
Language eng
Formatted abstract
Organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by Leishmania donovani. Experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. CD4+ T cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. In this study, we show that dendritic cells are critical for CD4+ T cell activation and expansion in all tissue sites examined. We found that FTY720-mediated blockade of T cell trafficking early in infection prevented Ag-specific CD4+ T cells from appearing in lymph nodes, but not the spleen and liver, suggesting that early CD4+ T cell priming does not occur in liver-draining lymph nodes. Extended treatment with FTY720 over the first month of infection increased parasite burdens, although this associated with blockade of lymphocyte egress from secondary lymphoid tissue, as well as with more generalized splenic lymphopenia. Importantly, we demonstrate that CD4+ T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens. Finally, although early CD4+ T cell priming appeared to occur most effectively in the spleen, we unexpectedly revealed that protective CD4+ T cell-mediated hepatic immunity could be generated in the complete absence of all secondary lymphoid tissues.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
 
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