Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs.
IL-15 is crucial for the development of intestinal intraepithelial lymphocytes (IEL) and delivery is mediated by a unique mechanism known as trans-presentation. Parenchymal cells have a major role in the trans-presentation of IL-15 to IELs, but the specific identity of this cell type is unknown. To investigate whether the intestinal epithelial cells (IEC) are the parenchymal cell type involved, a mouse model that expresses IL-15Ralpha exclusively by the IECs (Villin/IL-15Ralpha Tg) was generated. Exclusive expression of IL-15Ralpha by the IECs restored all the deficiencies in the CD8alphaalpha(+)TCRalphabeta(+)and CD8alphaalpha(+)TCRgammadelta(+) subsets that exist in the absence of IL-15Ralpha. Interestingly, most of the IEL recovery was due to the preferential increase in Thy1(low) IELs, which compose a majority of the IEL population. The differentiation of Thy1(high)CD4(-)CD8(-) thymocytes into Thy1(-)CD8alphaalpha IELs was found to require IL-15Ralpha expression specifically by IECs and thus, provides evidence that differentiation of Thy1(low) IELs is one function of trans-presentation of IL-15 in the intestines. In addition to effects in IEL differentiation, trans-presentation of IL-15 by IECs also resulted in an increase in IEL numbers that was accompanied by increases in Bcl-2, but not proliferation. Collectively, this study demonstrates that trans-presentation of IL-15 by IECs alone is completely sufficient to direct the IL-15-mediated development of CD8alphaalpha(+) T cell populations within the IEL compartment, which now includes a newly identified role of IL-15 in the differentiation of Thy1(low) IELs.
Ma
Lisa J
LJ
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Acero
Luis F
LF
Zal
Tomasz
T
Schluns
Kimberly S
KS
D000818:Animals; D017951:Antigen Presentation; D016827:CD8 Antigens; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology*; D053720:Interleukin-15 Receptor alpha Subunit / Q000172:deficiency / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013950:Thymus Gland / Q000166:cytology
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit