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Dependency on intercellular adhesion molecule recognition and local
interleukin-2 provision in generation of an in vivo CD8+ T-cell immune
response to murine myeloid leukemia
MW Boyer, PJ Orchard, KB Gorden, PM Anderson, RS Mclvor and BR Blazar
Department of Pediatrics, University of Minnesota Hospital and Clinic,
Minneapolis 55455, USA.
The immune response to a murine myeloid leukemia (cell line C1498) was
studied in vitro and in vivo. Natural killer (NK) cells and CD8+ cytotoxic
T lymphocytes (CTL) were shown to lyse C1498 in vitro through the binding
of leukocyte function antigen-1 (LFA-1) on effectors and intercellular
adhesion molecule-1 (ICAM-1) and ICAM-2 on C1498 target cells. However, the
ability of nonimmunized mice to resist an in vivo challenge of a low dose
(10(4)) of C1498 was NK-cell, but not T-cell dependent. The failure of T
cells to participate in the immune surveillance of a low leukemia burden
appeared, in part, because of a lack of expansion of leukemia reactive CTL
precursors (CTLp). Leukemia reactive CTLp frequency estimations in naive
and leukemia bearing mice were not significantly different (range, 1:20,600
to 1:74,000) in contrast to immunized mice (range, 1:1,400 to 1:4,400).
Leukemia reactive CTLp could be expanded to a level that could apparently
mediate in vivo immune surveillance of 10(5) leukemia cells by injection of
irradiated leukemia cells intraperitoneally (IP) or subcutaneously (SC),
but not intravenously (IV). However, IV injection of 10(5) live leukemia
cells engineered to secrete interleukin-2 (IL-2) resulted in systemic
immunity mediated primarily by CD8+ T cells. We conclude that NK cells can
mediate immune surveillance of a low leukemia burden. CD8+ CTL-mediated
immune surveillance can eliminate a higher leukemia burden than NK cells,
but requires T-cell help, which can be delivered by local IL-2. Both NK and
CTL-mediated immune surveillance of C1498 murine myeloid leukemia is
dependent on recognition through the LFA-1:ICAM adhesion pathway.
Volume 85,
Issue 9,
pp. 2498-2506,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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