CD28 expression redefines thymocyte development during the pre-T to DP transition

Int Immunol. 2010 May;22(5):387-97. doi: 10.1093/intimm/dxq020. Epub 2010 Mar 4.

Abstract

CD27 and CD28 have emerged as indicators demarcating the transition of thymocytes through beta-selection. We found that CD28 exhibits a greater dynamic range of expression during this phase, thus it was employed to further parse the DN/CD44(-) compartment in order to assess IL-7 signaling during the beta-selection process. Plotting CD28 versus CD25 expression revealed six DN/CD44(-) populations. OP9-DL1 stromal cell co-culture was used to demonstrate a developmental linkage from DN3a (CD25(+)CD28(-/lo)) to DN3b (CD25(+)CD28(+)) to DN3c (CD25(int)CD28(+)) to DN4a (CD25(-)CD28(+)) to double positive (DP) and showed the DN4b (CD25(-)CD28(hi)) and DN4c (CD25(-)CD28(-/lo)) populations to be inefficient in producing DP cells. Using CD69 as an additional marker to further parse the DN4a population, we found the pre-DP cells to be the CD44(-)CD25(-)CD28(int)CD69(-)CD4(-/lo)CD8(-/lo) subset. Using this refined developmental scheme, IL-7R alpha expression was found to be transiently up-regulated post-beta-selection in the DN3b and DN3c subsets; however, this increase did not confer enhanced responsiveness over that observed in the DN3a population. CD28 messenger RNA expression was up-regulated in post-beta-selected cells, whereas transcripts for CD27, IL-7R alpha and Bcl-2 were lower than that observed in the DN3a population. This study refines the current thymocyte differentiation scheme to allow for more detailed evaluation of events controlling early T-cell development, specifically surrounding the beta-selection checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • CD28 Antigens / genetics*
  • CD28 Antigens / immunology*
  • Cell Differentiation* / immunology
  • Coculture Techniques
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Humans
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lectins, C-Type / genetics
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Receptors, Interleukin-7 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD69 antigen
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain