Expression of CCR9 beta-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8(+) T cells from secondary lymphoid organs

Chemokines appear to have an important role in the seeding of lymphoid prog enitors in the thymus, the regulation of the coordinated movements of the m aturing T cells within this organ, end the egress of the resulting naive T cells to secondary lymphoid organs. CCR9, the specific receptor for the bet a -chemokine TECK/CCL25, is selectively expressed in thymus, lymph node, an d spleen. Using a specific anti-CCR9 polyclonal antibody, K629, and a semiq uantitative reverse transcriptase-polymerase chain reaction procedure, a de tailed study of CCR9 expression in the thymus and secondary lymphoid organs was performed. The results show that CD4(+)CD8(+) double-positive thymocyt es have the highest CCR9 expression in thymus. Single-positive CD8(+) thymo cytes continue to express this receptor after abandoning the thymus as matu re naive T cells, as suggested by the existence of a CD8(+)CD69(low)CD62L(h igh)CCR9(+) cell subset. Consistent with this, CD8(+) lymphocytes from lymp h nodes, spleen, and Peyer patches express a functional CCR9, as its expres sion correlates with migration in response to CCL25. Conversely, CD4(+) thy mocytes lose CCR9 before abandoning the thymus, and CD4(+) T cells from sec ondary lymphoid organs also lack CCR9 expression. Analysis of CCR9 expressi on in thymocytes from mice of different ages showed that CCR9 levels are af fected by age, as this receptor is more abundant, and its response to CCL25 is more potent in newborn animals. Collectively, these results suggest tha t CCR9 has a role in thymocyte development throughout murine life, with cle ar differences between the CD4(+) and CD8(+) lineages. (C) 2001 by The Amer ican Society of Hematology.