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Department of Pathology, University of Utah, Salt Lake City, UT 84112
Naive T cells have the capacity to expand in a lymphopenic environment in a process called homeostatic expansion, where they gain a memory-like phenotype. Homeostatic expansion is dependent on competition for a number of factors, including growth factors and interactions with their selecting self-MHC molecules. In contrast to conventional T cells, it is unclear whether class Ib-restricted CD8+ T cells have a capacity to undergo homeostatic expansion. In this study, we demonstrate that polyclonal MHC Ib-restricted CD8+ T cells can undergo homeostatic expansion and that their peripheral expansion is suppressed by conventional MHC-restricted T cells. The acute depletion of CD4+ T cells in MHC class Ia-deficient Kb–/–Db–/– mice led to the substantial expansion of class Ib-restricted CD8+ T cells. Adoptive transfer of class Ib-restricted CD8+ T cells to congenic lymphopenic recipients revealed their ability to undergo homeostatic expansion in a MHC Ib-dependent manner. To further study the homeostatic expansion of MHC Ib-restricted T cells in the absence of all conventional MHC-restricted T cells, we generated mice that express only MHC Ib molecules by crossing H-2Kb–/–Db–/– with CIITA–/– mice. CD8+ T cells in these mice exhibit all of the hallmarks of naive T cells actively undergoing homeostatic expansion with constitutive memory-like surface and functional phenotype. These findings provide direct evidence that MHC Ib-restricted CD8+ T cells have the capacity to undergo homeostatic expansion. Their peripheral expansion is suppressed under normal conditions by a numerical excess of conventional MHC class Ia- and class II-restricted T cells.
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1 This work was supported by National Institutes of Health Grants AI33614, AI20554 (to P.E.J.), and AI055434 (to D.C.J.).
2 D.C.J. and L.M.R.-L. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Peter E. Jensen, Department of Pathology, University of Utah, 30 North 1900 East, Room 5C124, Salt Lake City, UT 84132. E-mail address: peter.jensen{at}path.utah.edu
4 Abbreviations used in this paper: Treg, regulatory T cell; MHC II, MHC class II; iNKT, invariant NKT; hsp60, heat shock protein 60.
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