Selection of intestinal intraepithelial lymphocyte T cell receptors: evidence for a dynamic tissue-specific process

An extensive comparison of TCRαβ V-reglon usage by CD8β-CD4+CD8+ intraepithelial lymphocytes (IEL), CD4-CD8+ IEL, and lymph node (LN) T cell subsets in three minor lymphocyte stimulating (MIs)-disparate, MHC-ldentical mouse strains revealed novel TCR selection patterns. In cases where forbidden V regions were expressed by CD8β- CD4-CD8+ IEL, the same TCRs were deleted from CD8β− CD4+CD8+ IEL, Indicating that lack of CD8β expression was not solely responsible for forbidden V-region expression. These results also suggested that CD4 may be involved in negative selection of CD4+CD8+ IEL TCRs. In C57BR/cdJ (Mls-1b2b) mice, a major increase in Vβ3+CD4+CD8+ IEL but not in other IEL or LN subsets was noted suggesting a subset-specific expansion of Vβ3+ cells. Negative selection of Vβ14+ cells in only the CD4+CD8+ IEL subset further supported the existence of intestine-specific TCR selection processes. Analysis of V-reglon expression of CD8β+ and CD8β−CD4−CD8+ IEL subsets revealed that forbidden V-region expression was not strictly confined to the CD8β− subset in all cases. Overall, the data point to a dynamic, gut-specific TCR selection process that may be antigen driven.