T lymphocytes are not the target for estradiol-mediated suppression of DTH in reconstituted female severe combined immunodeficient (SCID) mice

Abstract

Oestrogen has the capacity to suppress T cell-dependent DTH. To explore the mechanisms whereby oestrogen exerts its effects on the immune system we have used SCID mice which are largely devoid of functional T and B lymphocytes, hence being unable to raise DTH, but display intact antigen-presenting capacity. Transfer of lymphocytes to SCID mice restores the DTH capacity. In order to analyse if oestrogen down-regulates DTH by a direct action on T cells we reconstituted SCID mice with either splenocytes or thymocytes from congenic C.B-17 or allogeneic B6 donor mice. Either donor or recipient mice were exposed to estradiol before cell transfer. DTH response was registered in recipient SCID mice 1 and 3 weeks after challenge with oxazolone (OXA). SCID mice receiving estradiol-exposed spleen cells from congenic or allogeneic donor mice displayed lower DTH responses compared with control mice. In contrast, SCID mice receiving estradiol-exposed thymocytes from congenic donor mice showed no significant difference in DTH response compared with control mice. Estradiol-treated SCID mice, transferred with either spleen cells or thymocytes from congenic, hormonally non-treated donors, displayed a significantly lower DTH response compared with control mice. In contrast, estradiol-treated SCID mice receiving hormonally non-treated allogeneic spleen cells showed no difference in DTH response compared with control mice. The results show that T lymphocytes are not the target cell population for estradiol-mediated suppression of DTH in reconstituted female SCID mice.

Up-regulation of TNF-producing T cells in the bone marrow: A key mechanism by which estrogen deficiency induces bone loss in vivo

“…We found that, at 4 weeks, spleen T cells were 2.0 Ϯ 0.2% in control nude mice and 8.6 Ϯ 0.3% in T cell-reconstituted mice (P Ͻ 0.05). Similar numbers of spleen T cells have been found by others after T cell reconstitution (14,15). Thus, the data establish that our procedure was effective in reconstituting T cells in nude mice.…”

“…T cells (1 ϫ 10 7 ) then were injected i.v. into the lateral tail vein of allotype-congenic C57BL͞6 nude recipients by using established methods (14,15). On the same day, T cell-reconstituted mice were subjected to either ovx or sham operation.…”

Modulatory effects of estrogen in two murine models of experimental colitis

“…Innate immunity and macrophages have, therefore, been suggested to play a role (17). Estrogen has been reported to suppress T cell-dependent DTH and activation of inflammatory cells producing TNF-␣ and IFN-␥ (51)(52)(53)58). Our data suggest a downregulation of the Th1 response associated to DNB colitis as reflected by decreased IFN-␥ mRNA expression 14 days postcolitis in 17␤-estradiol-treated mice.…”

Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α

“…The existence of such a regulatory mechanism has been described in models of T cell-mediated delayedtype hypersensitivity, where estrogen has been found to suppress T-cell proliferation through targeting of antigen-presenting cells (51,52). Similarly, previous reports from our laboratory demonstrated that estrogen represses stromal cell-soluble M-CSF production through targeting of IL-1-and TNF-producing bone marrow cells, rather than through a direct effect on mature stromal cells (16,27).…”