T-helper cells regulate the formation and function of specialized dendritic cell subsets in inflamed tissue : implications for multiple sclerosis
Abstract/Contents
- Abstract
- In multiple sclerosis and many other autoimmune diseases, activated T-helper (Th) cells colocalize with monocytes and dendritic cells (DC) in the inflamed tissue. Evidence suggests that these activated Th cells may be driving monocytes to differentiate into DC, but this phenomenon has not been explored in vivo. Using various methods of activating T-cells in vivo and the mouse model experimental autoimmune encephalomyelitis (EAE), we investigate how Th cells influence the function and phenotype of nearby monocytes. Using in vivo labeling of monocytes with a commercially available anti-CD209 antibody, we show that T-cell activation induces the rapid formation of monocyte-derived DC (Mo-DC) in lymph nodes. These T-cell driven Mo-DC are capable of robustly stimulating naïve T-cells, but induce little T-cell polarization. Surprisingly, TNF[alpha] but not GM-CSF was required for CD209+ Mo-DC formation after T-cell activation. These findings expand the range of signals capable of driving Mo-DC formation beyond known PAMPS and cytokines to include activated T-cells themselves. We also show that activated bulk Th cells or Th1, Th2 or Th17 subsets, when cultured with autologous monocytes in vitro, promote the formation of MHC II+, CD11b+, CD11c+ Mo-DC that we call DCTh. While all Th subsets tested induced the formation of DCTh, Th17 cells uniquely promoted the formation of IL-12/IL-23 producing Mo-DC with potent Th1 polarizing capacity that we call DCTh17. Further, Th cells isolated from the CNS of mice with Th17 driven EAE, drive robust formation of DCTh that produce IL-12 and polarize naive T-cells toward a Th1 phenotype. These results show that DCTh17 are critical in the interplay of Th17 and Th1 mediated responses in EAE and have implications for the treatment of MS.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Davidson, Matthew Gene |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Engleman, Edgar G |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Contag, Christopher H |
| Thesis advisor | Lee, Peter |
| Thesis advisor | Steinman, Lawrence |
| Advisor | Contag, Christopher H |
| Advisor | Lee, Peter |
| Advisor | Steinman, Lawrence |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Matthew Gene Davidson. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Matthew Gene Davidson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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