S. Gurunathan et al., Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: A potential immunoregulatory role for CD8(+) T cells, J IMMUNOL, 165(2), 2000, pp. 915-924
Protective immunity against Leishmania major generated by DNA encoding the
LACK (Leishmania homologue of receptor for activated C kinase) Ag has been
shown to be more durable than vaccination with LACK protein plus IL-12. One
mechanism to account for this may be the selective ability of DNA vaccinat
ion to induce CD8(+) IFN-gamma-producing T cells. In this regard, we previo
usly reported that depletion of CD8(+) T cells in LACK DNA-vaccinated mice
abrogated protection when infectious challenge was done 2 wk postvaccinatio
n, In this study, we extend these findings to study the mechanism by which
CD8(+) T cells induced by LACK DNA vaccination mediate both short- and long
-term protective immunity against L, major, Mice vaccinated with LACK DNA a
nd depleted of CD8(+) T cells at the time of vaccination or infection were
unable to control infection when challenge was done 2 or 12 wk postvaccinat
ion, Remarkably, it was noted that depletion of CD8(+) T cells in LACK DNA-
vaccinated mice was associated with a striking decrease in the frequency of
LACK-specific CD4(+) IFN-gamma-producing T cells both before and after inf
ection. Moreover, data are presented to suggest a mechanism by which CD8(+)
T cells exert this regulatory role. Taken together, these data provide add
itional insight into how Th1 cells are generated and sustained in vivo and
suggest a potentially novel immunoregulatory role for CD8(+) T cells follow
ing DNA vaccination.