Does TNF-α regulate thymic T cell developmental block in mice with dysregulated expression of Ly-6A?

Abstract

Abstract Ly-6A is a 12 kD GPI anchored member of the Ly-6 superfamily. Ly-6A and other gene family members show broad tissue expression, including expression on T lymphocytes. Ly-6A has been characterized as a cell adhesion molecule and shown to regulate cell signaling in T cells; specifically cytokine secretion. Published work indicates that this protein’s role in signaling regulation extends as far as mediated cell death pathways, resulting in growth arrest and ultimately cell death in T cell lines. Expression of Ly-6A on T cells in the thymus is developmentally regulated. Peak expression occurs during early stages of development, diminishes during maturation, and reappears at low levels on mature, CD4+ T cells. T lymphocytes in the thymus of Ly-6A transgenic (overexpressing) mice have been observed to experience increased instances of cell death and arrested early stage development. However, the underlying mechanisms of reduced cellularity in Ly-6A transgenic mice is unknown. I hypothesized that TNFα, a cytokine known to have cell death inducing properties, contributes to inhibited T cell development, lower cellularity and extensive cell death of developing T cells in thymi of Ly-6A transgenic mice. To address my hypothesis, I investigated the levels of TNFα in normal and Ly-6A transgenic mice. I find that there is decrease in cellularity in the developing thymus of Ly-6A transgenic mice compared to Ly-6A wildtype mice, consistent with published reports. On a per cell basis, this finding corresponds with increased TNFα release from Ly-6A transgenic T-lymphocytes. We plan to investigate development of T cells in Ly-6A transgenic mice that lack TNFα and specifically look for reversal of block in thymic T cell development.