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Blood, 1 November 2000, Vol. 96, No. 9, pp. 2973-2980
CHEMOKINES
T-lymphocyte production of macrophage inflammatory protein-1
is critical to the recruitment of CD8+ T
cells to the liver, lung, and spleen during
graft-versus-host disease
Jonathan S. Serody,
Susan
E. Burkett,
Angela Panoskaltsis-Mortari,
Judith Ng-Cashin,
Eileen McMahon,
Glenn K. Matsushima,
Sergio A. Lira,
Donald N. Cook, and
Bruce R. Blazar
From the Departments of Medicine, Microbiology, and
Immunology, University of North Carolina School of Medicine, the
Lineberger Comprehensive Cancer Center, and the University of North
Carolina Neurosciences Center, Chapel Hill, NC; the Schering Plough
Research Institute, Kenilworth, NJ; and the Department of Pediatrics,
Division of Blood and Marrow Transplantation, University of Minnesota
Cancer Center, Minneapolis, MN.
To investigate the mechanism by which macrophage inflammatory
protein-1 (MIP-1) affects graft-versus-host disease (GVHD), the
expression and function of MIP-1 in 2 murine models of GVHD were
evaluated. In irradiated class I and class II disparate recipients, the
expression of messenger RNA (mRNA) and protein for MIP-1 was
significantly increased in GVHD target organs after transfer of
allogeneic lymphocytes compared to syngeneic lymphocytes. When lymphocytes unable to make MIP-1 were transferred, there was a
decrease in the production of MIP-1 in the liver, lung, and spleen
of bm1 (B6.C-H2bm1/By) and bm12
(B6.C-H2bm12/KhEg) recipients compared to the transfer of
wild-type splenocytes. At day 6 there was a 4-fold decrease in the
number of transferred CD8+ T cells in the lung and
approximately a 2-fold decrease in the number of CD8+ T
cells in the liver and spleen in bm1 recipients after transfer of
MIP-1-deficient (MIP-1 /) splenocytes compared to
wild-type (MIP-1+/+) splenocytes. These differences
persisted for 13 days after splenocyte transfer. In contrast, the
number of donor CD4+ T cells found in the liver and lung
was significantly increased after the transfer of
MIP-1/ compared to wild-type splenocytes in bm12
recipients from day 6 through day 10. Thus, the transfer of allogeneic
T cells was associated with the enhanced expression of MIP-1 in both
a class I and class II mismatch setting. However, the increased
expression only led to enhanced recruitment of CD8+, but
not CD4+, donor T cells. Production of MIP-1 by donor T
cells is important in the occurrence of GVHD and functions in a
tissue-dependent fashion.
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