Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity.
Subcutaneous immunization delivers antigen (Ag) to local Ag-presenting cells that subsequently migrate into draining lymph nodes (LNs). There, they initiate the activation and expansion of lymphocytes specific for their cognate Ag. In mammals, the structural environment of secondary lymphoid tissues...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-05-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC2680335?pdf=render |
| _version_ | 1818888117140062208 |
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| author | Melanie Greter Janin Hofmann Burkhard Becher |
| author_facet | Melanie Greter Janin Hofmann Burkhard Becher |
| author_sort | Melanie Greter |
| collection | DOAJ |
| description | Subcutaneous immunization delivers antigen (Ag) to local Ag-presenting cells that subsequently migrate into draining lymph nodes (LNs). There, they initiate the activation and expansion of lymphocytes specific for their cognate Ag. In mammals, the structural environment of secondary lymphoid tissues (SLTs) is considered essential for the initiation of adaptive immunity. Nevertheless, cold-blooded vertebrates can initiate potent systemic immune responses even though they lack conventional SLTs. The emergence of lymph nodes provided mammals with drastically improved affinity maturation of B cells. Here, we combine the use of different strains of alymphoplastic mice and T cell migration mutants with an experimental paradigm in which the site of Ag delivery is distant from the site of priming and inflammation. We demonstrate that in mammals, SLTs serve primarily B cell priming and affinity maturation, whereas the induction of T cell-driven immune responses can occur outside of SLTs. We found that mice lacking conventional SLTs generate productive systemic CD4- as well as CD8-mediated responses, even under conditions in which draining LNs are considered compulsory for the initiation of adaptive immunity. We describe an alternative pathway for the induction of cell-mediated immunity (CMI), in which Ag-presenting cells sample Ag and migrate into the liver where they induce neo-lymphoid aggregates. These structures are insufficient to support antibody affinity maturation and class switching, but provide a novel surrogate environment for the initiation of CMI. |
| first_indexed | 2024-12-19T16:48:01Z |
| format | Article |
| id | doaj.art-d98090f74cc44671a380abc5ef9a6cce |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-19T16:48:01Z |
| publishDate | 2009-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-d98090f74cc44671a380abc5ef9a6cce2022-12-21T20:13:36ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852009-05-0175e100010910.1371/journal.pbio.1000109Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity.Melanie GreterJanin HofmannBurkhard BecherSubcutaneous immunization delivers antigen (Ag) to local Ag-presenting cells that subsequently migrate into draining lymph nodes (LNs). There, they initiate the activation and expansion of lymphocytes specific for their cognate Ag. In mammals, the structural environment of secondary lymphoid tissues (SLTs) is considered essential for the initiation of adaptive immunity. Nevertheless, cold-blooded vertebrates can initiate potent systemic immune responses even though they lack conventional SLTs. The emergence of lymph nodes provided mammals with drastically improved affinity maturation of B cells. Here, we combine the use of different strains of alymphoplastic mice and T cell migration mutants with an experimental paradigm in which the site of Ag delivery is distant from the site of priming and inflammation. We demonstrate that in mammals, SLTs serve primarily B cell priming and affinity maturation, whereas the induction of T cell-driven immune responses can occur outside of SLTs. We found that mice lacking conventional SLTs generate productive systemic CD4- as well as CD8-mediated responses, even under conditions in which draining LNs are considered compulsory for the initiation of adaptive immunity. We describe an alternative pathway for the induction of cell-mediated immunity (CMI), in which Ag-presenting cells sample Ag and migrate into the liver where they induce neo-lymphoid aggregates. These structures are insufficient to support antibody affinity maturation and class switching, but provide a novel surrogate environment for the initiation of CMI.http://europepmc.org/articles/PMC2680335?pdf=render |
| spellingShingle | Melanie Greter Janin Hofmann Burkhard Becher Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. PLoS Biology |
| title | Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. |
| title_full | Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. |
| title_fullStr | Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. |
| title_full_unstemmed | Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. |
| title_short | Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. |
| title_sort | neo lymphoid aggregates in the adult liver can initiate potent cell mediated immunity |
| url | http://europepmc.org/articles/PMC2680335?pdf=render |
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