Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus.
Most T lymphocytes are generated within the thymus. It is unclear, however, how newly generated T cells relocate out of the thymus to the circulation. The present study shows that a CC chemokine CCL19 attracts mature T cells out of the fetal thymus organ culture. Another CC chemokine CCL21, which shares CCR7 with CCL19 but has a unique C-terminal extension containing positively charged amino acids, failed to show involvement in thymic emigration. Neonatal appearance of circulating T cells was defective in CCL19-neutralized mice as well as in CCR7-deficient mice but not in CCL21-neutralized mice. In the thymus, CCL19 is predominantly localized in the medulla including endothelial venules. These results indicate a CCL19- and CCR7-dependent pathway of thymic emigration, which represents a major pathway of neonatal T cell export.
Ueno
Tomoo
T
Division of Experimental Immunology, Institute for Genome Research, The University of Tokushima and Laboratory of Immune System Development, RIKEN Research Center for Allergy and Immunology, 3-18-15 Kuramoto, 770-8503, Tokushima, Japan.
Hara
Kyoko
K
Willis
Melissa Swope
MS
Malin
Mark A
MA
Höpken
Uta E
UE
Gray
Daniel H D
DH
Matsushima
Kouji
K
Lipp
Martin
M
Springer
Timothy A
TA
Boyd
Richard L
RL
Yoshie
Osamu
O
Takahama
Yousuke
Y
D000818:Animals; D000831:Animals, Newborn; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009500:Neutralization Tests; D009924:Organ Culture Techniques; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine