Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes
- S. Brian Wilson*,†,
- Sally C. Kent‡,
- Heidi F. Horton§,
- Andrew A. Hill§,
- Paul L. Bollyky¶,
- David A. Hafler‡,
- Jack L. Strominger‖, and
- Michael C. Byrne§,†
- *Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115; ‡Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115; §Genetics Institute, Cambridge, MA 02140; ¶Harvard Medical School, Boston, MA 02115; and ‖Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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Contributed by Jack L. Strominger
Abstract
Quantitative and qualitative defects in CD1d-restricted T cells have been demonstrated in human and murine autoimmune diseases. To investigate the transcriptional consequences of T cell receptor activation in human Vα24JαQ T cell clones, DNA microarrays were used to quantitate changes in mRNA levels after anti-CD3 stimulation of clones derived from identical twins discordant for type 1 diabetes and IL-4 secretion. Activation resulted in significant modulation of 226 transcripts in the IL-4 secreting clone and 86 in the IL-4-null clone. Only 28 of these genes were in common. The differences observed suggest both ineffective differentiation of diabetic Vα24JαQ T cells and a role for invariant T cells in the recruitment and activation of cells from the myeloid lineage.
Footnotes
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↵ † To whom reprint requests should be addressed. E-mail: mbyrne{at}genetics.com (M.C.B.) or brian_wilson{at}dfci.harvard.edu (S.B.W.).
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See commentary on page 6933.
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Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.120161297.
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Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.120161297
- Abbreviations:
- Th,
- T helper;
- PI3-kinase,
- phosphoinositide-3-OH kinase;
- PMA,
- phorbol 12-myristate 13-acetate
- Copyright © The National Academy of Sciences
