Altered immune response in adult women exposed to diethylstilbestrol in utero

OBJECTIVE: Between 1940 and 1970, 1.5 million female fetuses were exposed to diethylstilbestrol in utero. Numerous deleterious effects on reproductive anatomic and physiologic characteristics have been documented in these women. However, the effects of this exposure on nonreproductive systems, which may have lifelong consequences as this cohort of women progresses beyond the childbearing years, have received little attention. On the basis of an earlier preliminary observation of altered immune reponse, we hypothesized that diethylstilbestrol-exposed women may show abnormalities in T-cell-mediated immune response. STUDY DESIGN: Thirteen women exposed to diethylstilbestrol in utero were compared with 13 age- and menstrual cycle phase-matched control subjects with respect to the in vitro T-cell response to the mitogens phytohemagglutinin, concanavalin A, and interleukin 2. RESULTS: As compared with controls, tritiated thymidine incorporation by T cells harvested from diethylstilbestrol-exposed women was increased 3-fold over a range of concentrations in response to concanavalin A (P <. 001), increased by 50% over a range of concentrations in response to phytohemagglutinin (P <. 001), and increased 2-fold in response to the endogenous mitogen interleukin 2 (P <. 05). CONCLUSIONS: In vitro evidence suggests that women exposed to diethylstilbestrol have alterations in T-cell-mediated immunity. These changes require further attention with regard to their characterization, their role in the pathogenesis of cancer and autoimmunity, and their presence in normal women exposed to diethylstilbestrol in utero.