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. 1991 Jun;73(2):186–190.

Analysis of the genetic encoding of oestradiol suppression of delayed-type hypersensitivity in (NZB x NZW) F1 mice.

H Carlsten 1, R Holmdahl 1, A Tarkowski 1
PMCID: PMC1384463  PMID: 2071164

Abstract

Oestrogen (E2) has been suggested to be responsible for the female preponderance for systemic lupus erythematosus (SLE) and for exacerbations of disease during pregnancy. In lupus-prone (NZB x NZW) F1 (NZB/W) mice, sex hormones also influence disease progression, thus long-term treatment of NZB/W mice with high doses of oestradiol increases the mortality in immune-complex mediated disease. We have previously demonstrated that E2 suppression of delayed-type hypersensitivity (DTH) to oxazolone (OXA) in NZB/W mice is inherited from the healthy NZW (H-2z) and not from the autoimmune NZB (H-2d) parental strain. In this paper we have analysed the influence of E2 on DTH and antibody responses to OXA in backcrosses of NZB/W mice and the NZB and NZW parental strains. Suppressed DTH was found in 15/16 (94%) of female (NZB/W x NZW) F1 (NZB/W/W) mice treated with E2. In contrast, only 32/36 (51%) of (NZB/W x NZB)F1 (NZB/W/B) mice treated with E2 displayed suppressed DTH reactivity. These two findings are compatible with a single, rather than multiple, dominant gene inherited from the NZW strain encoding for E2-mediated suppression of DTH in NZB/W mice. FACS analysis, using a monoclonal antibody recognizing the H-2z but not the H-2d locus, identified the H-2 expression (H-2dd and H-2dz) of the NZB/W/B backcrosses and revealed that E2 suppression of DTH is not linked to the H-2 haplotype of the backcrosses. Furthermore, E2 treatment of NZB/W/W mice, but not of NZB/W/B mice, significantly enhanced the serum levels of anti-OXA antibodies of both IgG and IgM classes. Based on our results it is tempting to speculate whether similar genetic factors for E2 sensitivity of the immune system may be of importance for the female predominance of human SLE.

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Selected References

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