Aims: 

Estrogen plays a critical role in the development and maintenance of immunity. Although estrogen is known to alter the gene transcription via binding to classical estrogen receptors (ER), it also exerts rapid non-transcriptional effects on intracellular signaling and consequently modulates cellular responses. Our aim was a) to compare the effect of estrogen on T-cell dependent (TD) and T-cell independent type 2 (TI-2) responses; and b) to analyze the non-classical effect of estrogen on intracellular signaling of B- and T-cells.

Methods: 

TD and TI response were evoked in mice by KLH-FITC and dextran-FITC conjugates, respectively. Antibody synthesis was tested by ELISA and ELISPOT.Activation of kinases was monitored by Western blot, intracellular [Ca²⁺] was measured by confocal microscopy.

Results: 

Ovariectomy significantly decreased, while estrogen re-administration increased the number of FITC-specific IgM and IgG producing cells in response to TD antigen. In contrast, ovariectomy had no effect on the response to TI-2 antigen. Estrogen induced activation of ERK1/2 and Akt kinases in vitro, furthermore, activated NFkB in both B- and T-cells; however, it stimulated a rise of intracellular free [Ca²⁺] only in T-cells. Both T and B cells expressed a putative plasma membrane ER, a potential mediator for the non-classical estrogen action. These non-transcriptional effects were mediated partly by classical estrogen receptors and partly by an as yet unidentified plasma membrane estrogen receptor. Such receptor- mediated rapid signals may modulate the in vivo the T cell-dependent immune response.

Conclusion: 

Our results provide the first evidence that estrogen enhances T-dependent but not the T-independent immune response in vivo. We have also shown that the estrogen-induced non-transcriptional effects are in part mediated by a yet unidentified plasma membrane ER.