Transgenic overexpression of the CC chemokine CCL21 disrupts T-cell migration.
Chemokines are a large family of cytokines that direct normal leukocyte migration. They also have been implicated in leukocyte development and in the pathogenesis of many diseases. The CC chemokine CCL21, also known as Exodus-2, SLC, 6Ckine, and TCA4 induces both the adhesion and migration of human T cells. CCL21 is hypothesized to regulate the trafficking of T cells through secondary lymphoid tissues. To test this hypothesis, a transgenic mouse model was generated that placed the expression of mouse CCL21 (mCCL21) under the control of the T cell-specific lck promoter to abrogate the concentration gradient to which T cells normally respond. Overexpression of mCCL21 in T cells resulted in defects in CCL21- and CCL19-induced T-cell chemotaxis, node T-cell subpopulations, and lymph node architecture. The regulation of T-cell trafficking in secondary lymphoid tissues by CCL21 is therefore a tightly regulated system that can be altered by changes in the level of environmental CCL21 protein.
Christopherson
K W
KW
Department of Biochemistry/Molecular Biology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis 46202, USA.
Campbell
J J
JJ
Hromas
R A
RA
D000818:Animals; D001402:B-Lymphocytes; D015153:Blotting, Western; D002448:Cell Adhesion; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D004247:DNA / Q000032:analysis; D015870:Gene Expression; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D016131:Lymphocyte Subsets; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000502:physiology*
C515478:CCL21 protein, human; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D004247:DNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)