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In vivo blockade of T cell development reveals alternative pathways for generation of intraepithelial lymphocytes in mice.
- Source :
-
Immunology letters [Immunol Lett] 2017 Nov; Vol. 191, pp. 40-46. Date of Electronic Publication: 2017 Sep 27. - Publication Year :
- 2017
-
Abstract
- Intraepithelial lymphocytes (IELs) are resident cells localized within the intestinal epithelia and play an important role in regulating gut inflammations and host defense against pathogens. CD8α <superscript>+</superscript> TCRαβ <superscript>+</superscript> IELs are heterogeneous populations that are generated from T cell precursors including CD4 <superscript>-</superscript> CD8α <superscript>-</superscript> double-negative (DN) cells and CD4 <superscript>+</superscript> CD8α <superscript>+</superscript> double-positive (DP) cells. However, developmental pathways of TCRαβ <superscript>+</superscript> IELs remained unclear. To gain insight into the mechanisms, we generated mice (Bcl11b <superscript>ΔDN2</superscript> mice) that lack thymic precursors (DN CD5 <superscript>+</superscript> TCRβ <superscript>+</superscript> cells) for CD4 <superscript>-</superscript> CD8αα <superscript>+</superscript> TCRαβ <superscript>+</superscript> IELs. Unexpectedly, we found that, in the absence of the precursors in thymi of Bcl11b <superscript>ΔDN2</superscript> mice, CD4 <superscript>-</superscript> CD8αα <superscript>+</superscript> TCRαβ <superscript>+</superscript> IELs were still present in the intestine though the number was reduced. Adoptive transfer experiment showed that their precursors were highly enriched in CD8α <superscript>+</superscript> TCRβ <superscript>-</superscript> thymocytes. The CD4 <superscript>-</superscript> CD8αα <superscript>+</superscript> TCRαβ <superscript>+</superscript> IELs in Bcl11b <superscript>ΔDN2</superscript> mice are distinguished by Thy1.2 expression and are indeed present in WT mice. Taken together, our study reveal a novel developmental pathway for CD8αα <superscript>+</superscript> TCRαβ <superscript>+</superscript> IELs.<br /> (Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adoptive Transfer
Animals
CD8 Antigens metabolism
Cell Differentiation
Cells, Cultured
Host-Pathogen Interactions
Immunophenotyping
Mice
Mice, Knockout
Receptors, Antigen, T-Cell, alpha-beta metabolism
Repressor Proteins genetics
Tumor Suppressor Proteins genetics
Intestinal Mucosa immunology
Intraepithelial Lymphocytes physiology
T-Lymphocyte Subsets physiology
Thymocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0542
- Volume :
- 191
- Database :
- MEDLINE
- Journal :
- Immunology letters
- Publication Type :
- Academic Journal
- Accession number :
- 28958836
- Full Text :
- https://doi.org/10.1016/j.imlet.2017.09.008