Estrogen in autoimmunity: expression of estrogen receptors in thymic and autoimmune T cells.
OBJECTIVE
To identify the targets of estrogen in immune system lymphocytes and to examine gender differences in autoimmunity.


METHODS
RNA samples from purified lymphocyte subsets were analyzed for the presence of mRNA for estrogen receptor alpha and beta (ER alpha and ER beta). Groups of male, female, and testicular-feminized mice were compared for autoantibody production.


METHODS
Autoimmune-prone lpr (Fas-deficient), testicular-feminized (Tfm, androgen receptor-deficient) and wild-type mice were studied.


METHODS
Lymphocyte subsets were purified by fluorescence-activated cell sorting (FACS) and RNA was assessed for the presence of estrogen receptor sequences using specific oligonucleotide primers and the reverse transcription-polymerase chain reaction (RT-PCR). Spontaneous and induced antibody production in mice was determined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
ER alpha was expressed in all lymphocyte subsets examined. ER beta was expressed at low levels in thymic CD4/CD8- T cells in wild-type mice and at high levels in the peripheral CD4-/CD8- T cells in lpr mice. Both spontaneous and induced autoantibody production was higher in female lpr mice than in male lpr mice.


CONCLUSIONS
The presence of ERs in lymphocytes indicates that estrogen may affect immune cells during their development and mature function. The selective expression of ER beta may help explain some of the physiological effects of estrogen and its pharmacologic analogues and may lead to means to direct estrogen analogues to such cells. Such effects may be explored in lpr mice, given the enhanced capacity of female lpr mice for autoantibody production.
Department of Neuropharmacology, Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
J
J
Törnwall
A B
AB
Carey
R I
RI
Fox
H S
HS
Fox
D013734:Androgen-Insensitivity Syndrome / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000378:metabolism*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D001323:Autoantibodies; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen