Tamoxifen prolongs heart allograft survival in cyclosporine-treated female mice

Zou, Yiping; Brandacher, Gerald; Obrist, Peter; Margreiter, Raimund; Steurer, Wolfgang

doi:10.1016/s0041-1345(98)01972-1

Cited by 2 publications

(2 citation statements)

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“…Previously, ovariectomies and the administration of tamoxifen, an inhibitor of the estrogen signaling machinery, have shown to prolong cardiac allograft survival. 32,53 Notably, more detailed clinical reports linking aging as a surrogate of estrogen levels with transplant outcomes and a more detailed analysis of estrogen levels affecting T cell alloimmune responses have been missing. Our data are filling the knowledge gap that aging and levels of female hormones impact alloimmune responses and graft loss.…”

Section: Discussionmentioning

confidence: 99%

“…We evaluated 407 963 recipients, dividing them into three age categories (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54), and 55-74 years, Figure 1). Clinical characteristics of donor/recipients assigned by age category are summarized in Table 1; time on dialysis, ABO-compatibility, HLA mismatches, ratios of either female or male donors, recipient/ donor BMI, donor age, deceased/living donor rates, and ethnicities were comparable per recipient age group; type II diabetes was more frequent in male versus female recipients in the age groups 35-54 and 55-74.…”

Section: Srtr Recipient Clinical Characteristicsmentioning

confidence: 99%

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Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion

Maenosono

Nian

Iske

et al. 2021

American Journal of Transplantation

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Sex‐specific influences have been shown for a variety of diseases. Whether donor or recipient sex and sex hormone levels impact alloimmune responses remains unclear. In unifactorial and multifactorial analyses of more than 400 000 SRTR listed kidney transplant patients, we found that younger female recipients had an inferior death‐censored graft survival that was independent of donor sex. In contrast, graft survival was superior in older female recipients, suggesting the impact of recipient sex hormones over chromosomal sex mismatches. Those clinical changes were delineated in experimental skin and heart transplant models showing a prolongation of graft survival in ovariectomized young female recipients. In contrast, graft survival was comparable in ovariectomized and naïve old female recipients. Young ovariectomized mice showed reduced amounts and a compromised T cell proliferation. Deprivation of female hormones dampened the production of interferon (IFN)‐γ and interleukin (IL)‐17+ by CD4+ T cells while augmenting systemic counts of Tregs. Increasing estradiol concentrations in vitro promoted the switch of naïve CD4+ T cells into Th1 cells; high physiological estradiol concentrations dampening Th1 responses, promoted Tregs, and prolonged graft survival. Thus, clinical observations demonstrate age‐specific graft survival patterns in female recipients. Estrogen levels, in turn, impact the fate of T cell subsets, providing relevant and novel information on age‐ and sex‐specific alloimmunity.

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Section: Discussionmentioning

confidence: 99%