A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8- triple-negative adult mouse thymocytes defined by CD44 and CD25 expression.
We have subdivided mouse CD4-CD8-CD3- triple-negative (TN) thymocytes into four subsets based upon expression of CD44 and CD25, including CD44+CD25-, CD44+CD25+, CD44-CD25+ and CD44-CD25-. Characterization of these cells revealed several features distinct to each subset, in particular the expression of high levels of c-kit (the receptor for stem cell factor) by CD44+CD25-TN and CD44+CD25+TN but not by CD44-CD25+TN and CD44-CD25-TN. The CD44+CD25+TN subset also included the IL-7 and stem cell factor-responsive cells, whereas only minimal responsiveness was observed by the CD44- populations. These subsets also showed differential cytokine production potential (CD44+CD25- > CD44+CD25+ > CD44-CD25+ > CD44-CD25-) after stimulation with calcium ionophore, PMA and IL-1. The repopulation potential of these subsets in 2-deoxyguanosine-treated fetal thymic lobes supports the following maturation sequence: CD44+CD25- -->CD44+CD25+ -->CD44-CD25+ -->CD44-CD25-. Furthermore, the sequence of progression from CD44+CD25+ to CD44-CD25+ cells was confirmed by their TCR beta-chain gene configuration. The former population exhibits germ-line TCR beta-chain configuration, whereas the latter subset shows a rearranged pattern.
DNAX Research Institute, Palo Alto, CA 94304.
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DI
Godfrey
J
J
Kennedy
T
T
Suda
A
A
Zlotnik
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing