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

Abstract

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-1^b2^b) mice, a major increase in V_β3⁺CD4⁺CD8⁺ IEL but not in other IEL or LN subsets was noted suggesting a subset-specific expansion of V_β3⁺ cells. Negative selection of V_β14⁺ 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.