Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter.
OBJECTIVE
Different conclusions have been reached in recent studies concerning the immune response or tolerance of transgenic (Tg) mice expressing foreign antigens under control of retinal antigen promoters. The present study was aimed at analyzing the state of tolerance in Tg mice expressing hen egg lysozyme (HEL) under control of the rhodopsin promoter.


METHODS
Tg mice expressing HEL under control of the rhodopsin promoter (RhHEL-Tg) were generated and tested by conventional methods for immune responses against HEL. These Tg mice were also mated with Tg mice expressing HEL-specific receptor on their T lymphocytes and the double-Tg mice were examined for increased apoptosis in their thymi by the TUNEL assay, as well as for loss of HEL-specific T cells, by flow cytometry and proliferative response. The presence of HEL mRNA in mouse thymi was determined by RT-PCR.


RESULTS
RhHEL-Tg mice developed tolerance to HEL, shown by reduced cellular and humoral responses to HEL, as well as by the failure of ocular inflammation to develop after immunization with HEL. RhHEL-Tg mice expressed HEL mRNA in their thymus, and the tolerogenic mechanism in these mice was shown to be thymic deletion of HEL-specific T cells by the following observations in the double-Tg mice: (1) increased apoptosis in their thymi, (2) remarkable reduction in the proportion of the HEL-specific T cells, and (3) loss of lymphocyte response to low concentrations of HEL.


CONCLUSIONS
Tg mice expressing HEL under control of the rhodopsin promoter develop a tolerance for the foreign antigen, apparently as a result of thymic expression of HEL and deletion of T cells specific to this antigen.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Don-Il
DI
Ham
Stephen J
SJ
Kim
Jun
J
Chen
Barbara P
BP
Vistica
Robert N
RN
Fariss
Robert S
RS
Lee
Eric F
EF
Wawrousek
Hiroshi
H
Takase
Cheng-Rong
CR
Yu
Charles E
CE
Egwuagu
Chi-Chao
CC
Chan
Igal
I
Gery
D000818:Animals; D000917:Antibody Formation; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D007108:Immune Tolerance; D007111:Immunity, Cellular; D020287:In Situ Nick-End Labeling; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000378:metabolism
D001324:Autoantigens; D012333:RNA, Messenger; D012243:Rhodopsin; C421864:hen egg lysozyme; D009113:Muramidase