Murine thymic selection quantified using a unique method to capture deleted T cells

Gretta L. Stritesky, Yan Xing, Jami R. Erickson, Lokesh A. Kalekar, Xiaodan Wang, Daniel L. Mueller, Stephen C. Jameson, Kristin A. Hogquist

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Thymic positive and negative selection events generate a T-cell repertoire that is MHC restricted and self-tolerant. The number of T cells undergoing positive and negative selection in normal mice has never been firmly established. We generated mice that lack the proapoptotic molecule Bim (bcl2l/1) together with a Nur77GFP transgene, which allowed the identification and enumeration of T cells that would normally undergo clonal deletion. Using this method, we report the striking observation that six times more cells undergo negative selection than complete positive selection. Seventy-five percent of the negatively selected cells are deleted at the double positive stage in the thymic cortex, compared with 25% at the single positive stage in the medulla. The fact that more thymocytes are highly reactive to MHC than are weakly reactive is inconsistent with a random model of recognition and suggests that T-cell recognition is MHC biased. Furthermore, Bim-/- mice had an increased number of GFPhi cells in the peripheral lymphoid tissue and a corresponding increase in antigen experienced or anergic cell phenotype. Our data also show that the CD4+ T cells that are clonally deleted experienced only slightly stronger T-cell receptor signaling than those that developed into regulatory T cells.

Original languageEnglish (US)
Pages (from-to)4679-4684
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number12
DOIs
StatePublished - Mar 19 2013

Keywords

  • Lymphocyte development
  • Thymus

Fingerprint

Dive into the research topics of 'Murine thymic selection quantified using a unique method to capture deleted T cells'. Together they form a unique fingerprint.

Cite this