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Macrophage Inflammatory Protein-1 Induces Migration and
Activation of Human Thymocytes
Daniel J. Dairaghi,
Karin Franz-Bacon,
Eleni Callas,
James Cupp,
Thomas J. Schall,
Susan A. Tamraz,
Stefen A. Boehme,
Naomi Taylor, and
Kevin B. Bacon
From the Departments of Immunology and Molecular Biology, DNAX
Research Institute, Palo Alto, CA; the Department of Immunology,
Neurocrine Biosciences Inc, San Diego, CA; and the Institut de
Genetique Moleculaire, Montpellier, France.
The CC chemokine macrophage inflammatory protein 1 (MIP-1),
has been shown to be a chemoattractant preferentially activating CD4+ CD45RA+ T lymphocytes. Further
analysis of chemokine action on lymphocytic cells has shown the potent
migration-promoting capacity of MIP-1 on human thymocytes. The
responding cells were the CD4+ and CD8+
single-positive (SP), as well as the CD4+
CD8+ double-positive (DP) populations, with little if any
migratory activity on the double-negative (DN) population. The
activation of thymocytes by MIP-1 appeared to be a direct,
receptor-mediated event as evidenced by the rapid mobilization of
intracellular calcium, increase in proteins phosphorylated on tyrosine,
and activation of the mitogen-activated protein kinase (MAPK) pathway. Radioligand binding analyses showed specific and displaceable binding
of MIP-1 to thymocytes with a Kd of approximately 1 nmol/L, a
profile that was comparable with MIP-1 binding to CCR-5-transfected NIH 3T3 cells. In addition, CCR-5 mRNA was detected in total thymocyte populations indicating that activation of thymocytes by MIP-1 may
occur through binding to CCR-5. Further dissection of the subpopulations showed that only the DP and CD8+ SP
populations expressed CCR-5 and expression data on these two populations was confirmed using anti-CCR-5 monoclonal antibody. These
data may be suggestive of a role for MIP-1 in human thymocyte activation, and show a potential route for HIV infectivity in the
developing immune system.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2905-2913
© 1998 by The American Society of Hematology.
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