Endocrine and Other Influences on the Trafficking of Immune Cells
This dissertation examines endocrine and other influences on the trafficking of immune cells. This work aimed to increase the understanding of underlying mechanisms pertaining to immune cell entry into breast milk, and prolactin’s involvement in this important physiological phenomenon. Because of observations made during this study, the work also examined various aspects of sexual dimorphism in lymph nodes and thymus.
Luminal mammary epithelial cell secretions act as chemoattractants, inducing migration of a variety of lymphocytes, phagocytes, and granulocytes. Prolactin treatment of mammary epithelial cells increases production of chemoattractants and migration of most of these cell types. This supports a role for luminal mammary epithelial cells in immune cell concentration into milk. CCL2 and CXCL1 were two chemoattractants identified responsible for a significant degree of migration of monocytes and neutrophils, respectively. In-vivo prolactin treatment increased immune cell flux through the mammary tissue and increased expression of CCL2 and CXCL1 in a mammary cell line in vitro.
Female mice have more T-cells in their popliteal lymph nodes than males, while males have a greater proportion of T-cells that are suppressive in function. This combination supports a rationale for females having a higher delayed-type hypersensitivity response in a region drained by this lymph node. The sex difference in T-cells is present prior to puberty and is to some extent dependent on Sry expression as males overexpressing Sry have even fewer T-cells. In addition, male gonadal secretions amplified the sex difference as mice aged.
Adult female mice with two X chromosomes exhibit a greater delayed-type hypersensitivity response to Candida albicans at proestrus than at metestrus or diestrus, while females with an X and a Y chromosome, the latter minus the Sry gene, did not exhibit different responses across these stages of the estrous cycle. There is therefore a combined effect of the sex chromosomal complement and hormonal changes occurring at proestrus that permits maximal response.
These results demonstrate significant interactions between the endocrine and immune systems both in regions where one might expect (the mammary gland during lactation) and in regions (the popliteal lymph node) where gene and endocrine sex effects were not anticipated.