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Differential Chemotactic Behavior of Developing T Cells in Response
to Thymic Chemokines
Chang H. Kim,
Louis M. Pelus,
John R. White, and
Hal E. Broxmeyer
From the Departments of Microbiology/Immunology and Medicine and the
Walther Oncology Center, Indiana University School of Medicine,
Indianapolis, IN; the Walther Cancer Institute, Indianapolis, IN; and
the Departments of Molecular Virology and Host Defense and of Molecular
Immunology, SmithKline Beecham Pharmaceuticals, Collegeville, PA, and
King of Prussia, PA.
Differentiation-dependent thymocyte migration in the thymus may be
important for T lymphopoiesis and might be regulated by thymic
chemoattractants. We examined modulation of chemotactic responsiveness
of thymocyte subsets during their early to late stages of development
in response to 2 thymus-expressed chemokines, SDF-1 and
CK -11/MIP-3/ELC. SDF-1 shows chemotactic preference for immature
thymocytes (subsets of triple negative thymocytes and double positive
[DP] subset) over mature single positive (SP) thymocytes.
CK-11/MIP-3/ELC shows low chemotactic activity on the immature
thymocytes, but it strongly attracts mature SP thymocytes, effects
opposite to that of SDF-1. SDF-1-dependent chemoattraction of immature
thymocytes is not significantly desensitized by a negative
concentration gradient of CK-11/MIP-3/ELC, and chemoattraction of
mature SP thymocytes to CK-11/MIP-3/ELC is not antagonized by
SDF-1, demonstrating that these two chemokines have different chemoattractant preferences for thymocyte subsets and would probably not inhibit each other's chemotaxis in the event of microenvironmental coexpression. The chemotactic responsiveness of thymocytes and mature T
cells to the 2 chemokines is respectively enhanced after selection
process and migration to the spleen. These studies demonstrate the
presence of thymocyte chemoattractants with differential chemotactic preference for thymocytes, a possible mechanism for thymocyte migration
in the thymus.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4434-4443
© 1998 by The American Society of Hematology.
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