TY - JOUR
T1 - Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment
AU - Klug, David B.
AU - Carter, Carla
AU - Crouch, Elizabeth
AU - Roop, Dennis
AU - Conti, Claudio J.
AU - Richie, Ellen R.
PY - 1998/9/29
Y1 - 1998/9/29
N2 - Thymocyte and thymic epithelial cell (TEC) development are interdependent processes. Although lineage relationships among progressively maturing thymocyte subsets have been characterized, the developmental relationships among TEC subsets are obscure. Because epithelial cells express distinct keratin (K) species as a function of differentiation stage and proliferative status, we used K expression patterns to identify mouse TEC subsets and determine their lineage relationships. As expected, cortical and medullary TEC subsets express distinct K expression patterns in the normal thymus. However, we detected two distinct cortical TEC subsets, a major K8+K5- subset and a minor KS+K5+ subset, which is highly represented at the cortico-medullary junction. Both cortical TEC subsets are also present in recombination activating gene 1 (RAG-1(-/-)) and TCRβxδ(-/-) thymi in which T-cell development is blocked at the CD4-CD8-CD25+CD44- pre-T cell stage. In contrast, KS+K5+ TECs predominate in the thymi of human CD3ε transgenic mice in which thymocyte development is blocked at an earlier CD4-CD8-CD25- CD44+ stage. Transplantation of newborn human CD3ε transgenic thymi under the kidney capsule of RAG-1(-/-) mice results in the emergence of KS+K5- TECs concomitant with the appearance of CD25+ thymocytes. Together, the data suggest that cortical TEC development proceeds from a KS+K5+ precursor subset to a K8+K5- stage in a differentiation process concomitant with T- cell lineage commitment.
AB - Thymocyte and thymic epithelial cell (TEC) development are interdependent processes. Although lineage relationships among progressively maturing thymocyte subsets have been characterized, the developmental relationships among TEC subsets are obscure. Because epithelial cells express distinct keratin (K) species as a function of differentiation stage and proliferative status, we used K expression patterns to identify mouse TEC subsets and determine their lineage relationships. As expected, cortical and medullary TEC subsets express distinct K expression patterns in the normal thymus. However, we detected two distinct cortical TEC subsets, a major K8+K5- subset and a minor KS+K5+ subset, which is highly represented at the cortico-medullary junction. Both cortical TEC subsets are also present in recombination activating gene 1 (RAG-1(-/-)) and TCRβxδ(-/-) thymi in which T-cell development is blocked at the CD4-CD8-CD25+CD44- pre-T cell stage. In contrast, KS+K5+ TECs predominate in the thymi of human CD3ε transgenic mice in which thymocyte development is blocked at an earlier CD4-CD8-CD25- CD44+ stage. Transplantation of newborn human CD3ε transgenic thymi under the kidney capsule of RAG-1(-/-) mice results in the emergence of KS+K5- TECs concomitant with the appearance of CD25+ thymocytes. Together, the data suggest that cortical TEC development proceeds from a KS+K5+ precursor subset to a K8+K5- stage in a differentiation process concomitant with T- cell lineage commitment.
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U2 - 10.1073/pnas.95.20.11822
DO - 10.1073/pnas.95.20.11822
M3 - Article
C2 - 9751749
AN - SCOPUS:0032578456
SN - 0027-8424
VL - 95
SP - 11822
EP - 11827
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -