Parallel Expression of Enzyme Inhibitors of CD8T Cell Activity in Tumor Microenvironments and Secretory Endometrium.

The divergent requirement for tolerance to support conception and protective response against sexually transmitted infections defines the unique immunological dynamics in the female reproductive tract (FRT). In part, these requirements are achieved by the cyclic modulation of cytolytic CD8T cell function in the FRT that underlie the respective immunosuppressive and immunocompetent milieus during the secretory and proliferative phases of the menstrual cycle. The CD8T cell function can be dampened by exposure to indoleamine 2,3-dioxygenase and/or arginase enzymes. Indeed, these 2 enzymes are known as primary inducers of immune suppression in tumor microenvironments. This review discusses the intriguing parallel expression of these 2 enzymes in tumor microenvironments and in the secretory endometrium. We surmise that investigating the underlying natural mechanisms that suppress and restore the immunocompetence of CD8T cells in the FRT each month may provide valuable insights into ways to artificially recapitulate these mechanisms and inhibit immune suppression in tumor microenvironments.

Modulation of MICA on the surface of Chlamydia trachomatis-infected endocervical epithelial cells promotes NK cell-mediated killing.

Chlamydia trachomatis serovars D-K are obligate intracellular bacteria that have tropism for the columnar epithelial cells of the genital tract. Chlamydia trachomatis infection has been reported to induce modifications in immune cell ligand expression on epithelial host cells. In this study, we used an in vitro infection model that resulted in a partial infection of C. trachomatis-exposed primary-like immortalized endocervical epithelial cells (A2EN). Using this model, we demonstrated that expression of the natural killer (NK) cell activating ligand, MHC class I-related protein A (MICA), was upregulated on C. trachomatis-infected, but not on noninfected bystander cells. MICA upregulation was concomitant with MHC class I downregulation and impacted the susceptibility of C. trachomatis-infected cells to NK cell activity. The specificity of MICA upregulation was reflected by a higher cytolytic activity of an NK cell line (NK92MI) against C. trachomatis-infected cells compared with uninfected control cells. Significantly, data also indicated that NK cells exerted a partial, but incomplete sterilizing effect on C. trachomatis as shown by the reduction in recoverable inclusion forming units (IFU) when cocultured with C. trachomatis-infected cells. Taken together, our data suggest that NK cells may play a significant role in the ability of the host to counter C. trachomatis infection.

Recurrent first trimester pregnancy loss: revised definitions and novel causes.

PURPOSE OF REVIEW: First trimester pregnancy loss affects up to 15% of clinically recognized pregnancies. Whereas most couples will proceed to have successful subsequent pregnancies, 2-4% will suffer recurrent losses, often with no identifiable cause. In fact, up to 40-50% of patients suffering recurrent pregnancy loss (RPL) will have no identifiable cause for their losses. Whereas the high incidence of spontaneous fetal aneuploidy will ensure that this number will never fall to zero, its level suggests that additional causes and appropriate diagnostic testing await discovery. The definition, diagnostic work-up and appropriate interventions among patients with RPL remain controversial. Here, we will review those papers published in the last 1-2 years that improve our understanding of the definition of RPL, that confirm the utility of present testing paradigms or that pose novel causes and diagnostic approaches to patients with a history of RPL. RECENT FINDINGS: Standard definitions of RPL have been suggested by the American Society of Reproductive Medicine. Suggested potential diagnostic testing for RPL has been expanded to include male factors and new paradigms that address placental function, including the role of vascular endothelial growth factor, thrombosis and maternal-fetal immunology. SUMMARY: Standardized definitions for RPL and standardized approaches to initiating the RPL work-up will aid in study design and improve the applicability and implications of published findings. Appropriate investigation of novel causes for RPL may decrease the percentage of patients carrying the diagnosis of unexplained RPL.