Arch Virol (2004) 149: 2235–2244
Perforin knockout mice, but not mice with MAIDS, show
protection against experimental cytomegalovirus retinitis
after adoptive transfer of immune cells with a functional
perforin cytotoxic pathway
R. D. Dix
, C. O. Ekworomadu
, E. Hernandez
, and S. W. Cousins
Department of Ophthalmology, Harvey & Bernice Jones Eye Institute, University
of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
Department of Microbiology and Immunology, Harvey & Bernice Jones Eye
Institute, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A.
Department of Ophthalmology, Bascom Palmer Eye Institute, University
of Miami School of Medicine, Miami, FL, U.S.A.
Received April 13, 2004; accepted May 14, 2004
Published online July 15, 2004
Summary. Adoptive transfer studies were performed to test the hypothesis that
the perforin cytotoxic pathway is more important than the Fas/FasL cytotoxic
pathway in protection against experimental murine cytomegalovirus (MCMV)
retinitis. Splenic immune cells from donor MCMV-immunized normal mice or
gld mice deﬁcient in Fas/FasL-mediated cytotoxicity signiﬁcantly reduced the
frequency and severity of MCMV retinitis following subretinal MCMV chal-
lenge when transferred into recipient PKO mice deﬁcient in perforin-mediated
cytotoxicity. In sharp contrast, splenic cells from donor MCMV-immunized PKO
mice failed to provide protection against MCMV retinitis when transferred into
recipient PKO mice. Protection was not achieved, however, in recipient mice
with retrovirus-induced immunodeﬁciency (MAIDS), even when splenic cells
originated from MCMV-immunized normal mice.
Human cytomegalovirus (HCMV) retinitis continues to be a signiﬁcant ophthal-
mologic complication in patients immunosuppressed by human immuno-
deﬁciency virus type 1 (HIV-1) infection even in the present era of highly active
antiretroviral therapy (HAART) . In fact, the incidence of HCMV retinitis