Abstract
Innate memory phenotype (IMP) CD8+ T cells are nonconventional αβ T cells exhibiting features of innate immune cells and are significantly increased in the absence of ITK. Their developmental path and function are not clear. In this study, we show hematopoietic MHC class I (MHCI)-dependent generation of Ag-specific IMP CD8+ T cells using bone marrow chimeras. Wild-type bone marrow gives rise to IMP CD8+ T cells in MHCI−/− recipients, resembling those in Itk−/− mice, but distinct from those derived via homeostatic proliferation, and independent of recipient thymus. In contrast, MHCI−/− bone marrow does not lead to IMP CD8+ T cells in wild-type recipients. OTI IMP CD8+ T cells generated via this method exhibited enhanced early response to Ag without prior primary stimulation. Our findings suggest a method to generate Ag-specific “naive” CD8+ IMP T cells, as well as demonstrate that they are not homeostatic proliferation cells and can respond promptly in an Ag-specific fashion.
Footnotes
This work was supported by grants from the National Institutes of Health (AI051626 and AI065566) to A.A.
The sequences presented in this article have been submitted to the National Center for Biotechnology Information’s Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE41482.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- BMT
- bone marrow transplantation
- HP
- homeostatic proliferation
- IMP
- innate memory phenotype
- MHCI
- MHC class I
- P/I
- PMA and ionomycin
- WM
- WT→MHC−/−
- WT
- wild-type.
- Received November 1, 2012.
- Accepted January 15, 2013.
- Copyright © 2013 by The American Association of Immunologists, Inc.