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Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan
We investigated the effects of IL-18 on the development of
CD8+ effector T cells in DBA/2
anti-BDF1 whole spleen cell MLC and compared the
results with those of IL-12. Addition of IL-18 to the MLC resulted in a
twofold increase in CD8/CD4 ratios compared with the control cultures
when cells were expanded in IL-2-containing medium following MLC.
Purified CD8+ T cells recovered from the IL-18-stimulated
MLC produced 20- to 30-fold more IFN-
after secondary stimulation
with C57BL/6 spleen cells or anti-CD3 mAb, and exhibited strong
allospecific CTL activity. Neither IL-18 nor IL-18-supplemented culture
supernatants from DBA/2 anti-BDF1 MLC induced type I
CD8+ effector T cells when purified CD8+ T
cells were used as responder cells in primary MLC. Furthermore,
CD4+ T cell depletion from the responder cells abrogated
the IL-18-induced increase in secondary IFN- production by
CD8+ T cells, suggesting that IL-18-induced type I effector
CD8+ T cell development was CD4+ T cell
dependent. In marked contrast, adding IL-12 to primary MLC decreased
CD8/CD4 ratios by 50% and suppressed secondary IFN- production and
CTL activity by CD8+ T cells regardless of concentration,
whereas Th1 development was promoted by IL-12. Moreover, both IL-12 and
IL-18 efficiently induced type I CD8+ effector T cells in
C57BL/6 anti-BDF1 MLC. These findings show that IL-18
plays an important role in the generation of type I CD8+
effector T cells, and further suggest that functional maturation of
CD8+ T cells is differentially regulated by IL-18 and
IL-12.
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