Christine A. Rasmussen

Granulocyte/macrophage-colony-stimulating factor released by adenovirally transduced CT26 cells leads to the local expression of macrophage inflammatory protein 1α and accumulation of dendritic cells at vaccination sites in vivo

Abstract Antigen presenting cells (APC) play an essential role in the generation of tumor-specific immune responses. Dendritic cells are the most potent of APC, capable of activating both antigen-specific CD4+ and CD8+ T cells. Previously, we have described how vaccination of mice with irradiated tumor cells producing granulocyte/macrophage-colony-stimulating factor (GM-CSF) induces tumor-specific immunity capable of protecting mice from a subsequent tumor challenge. The present study extends these findings to examine the types of APC infiltrating vaccination sites and the chemokines responsible for their recruitment. GM-CSF released from genetically engineered tumor cells led to the local accumulation of dendritic cells in and around the vaccination site. Quantification revealed a significant ten-fold increase in the number of dendritic cells infiltrating GM-CSF-producing as opposed to β-galactosidase-producing (control) vaccination sites. Reverse transcription/polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis of vaccination sites revealed that MIP-1α may be responsible for dendritic cell infiltration into GM-CSF-producing tissues. These findings suggest that GM-CSF may indirectly recruit dendritic cells into vaccination sites through the local production of MIP-1α.

Apoptosis-inducing members of the tumor necrosis factor supergene family: Potential functions in placentae

Summary Apoptosis-inducing members of the TNF supergene family are clearly involved in local maternal-fetal immunological relationships as well as placental development and function. Although significant progress has been made in mapping out the temporal and spatial distribution of the best known members of this powerful gene family, TNFα, LTα and FasL, many newly reported ligands and receptors have yet to be examined. Furthermore, it is not yet clear how broad the range of functions of these cytokines may be or whether their death-dealing property is the most important. Nor is it certain whether each factor has an individual, specific role or whether overlapping functions will be the rule. Although developing a full understanding of the cytokines that comprise this family is a daunting task as greater and greater complexities are revealed, sorting out the expression, regulation and activities of each could yield major benefits. Infertility in one in six couples is now a widely quoted figure ( ISLAT Working Group, 1998 ) and it is likely that some portion of reproductive failure is due to inappropriate PCD and ACD mediated by members of the TNF supergene family.

Decidual signals in the establishment of pregnancy: The prolactin family

Summary Decidual cells are responsible for creating a uterine environment supportive of the development of extraembryonic and embryonic tissues. A hormone family structurally related to pituitary PRL is a component of the efferent decidual cell response. Thus far, members of the PRL gene family have been identified in primates and in the rat. Patterns of expression during gestation suggest a role for members of the decidual PRL family in the establishment and maintenance of the gestational state. Precise physiological roles for each member of the decidual PRL family remain to be elucidated.

The tumor necrosis factor gene family in pregnancy

Summary Even though many cytokines and growth factors first identified in the immune system are now known to participate in reproductive processes, investigators have been slow to recognize and evaluate the potential involvement of TNF family members. Yet recent studies illustrate the probability that several members of this family are important, particularly TNFα, LTα, CD30 and LTβ. The amn, gld and lpr mutant mouse strains, transgenic mice made deficient in TNF superfamily members and their receptors by gene targeting in embryonic stem cells as well cell lines developed from these mice should be extremely useful in learning how these potent, pleiotrophic cytokines contribute to successful pregnancy.