A Y-chromosome factor impairs iNKT cell development (85.15)

Abstract

Abstract Invariant Natural Killer T (iNKT) cells are a fairly recently discovered unique subset of T lymphocytes. These granular cells are derived from the thymus and share properties of both NK and T cells. iNKT cell development is unique from mainstream T cell selection and the polygenic factors that influence NK T cell ontogeny are still unclear. Previous studies done in our laboratory has shown the absence of iNKT cells in male B6.IFN-αβR1-/- mice. Analysis of the iNKT cell compartment in a variety of mice demonstrated that the deficiency was linked to the Y-chromosome but independent of IFN-αβ. Here, we generated wild-type male B6 mice carrying the YNKT-chromosome as well as male B6.IFN-αβR1-/- mice that do not carry the YNKT-chromosome. We found that wild-type B6 (YNKT) male mice have a strong decrease in iNKT cell frequency. In contrast, the B6.IFN-αβ R1-/- male mice have a relatively normal repertoire, confirming that the deficiency is linked to the Y-chromosome and is independent of IFN-α/β In addition, preliminary data using two different strains of B6 consomic mice for the Y-chromosome show that they have a normal iNKT cell repertoire. This suggests that a consomic Y chromosome is not sufficient to influence iNKT cell development. We are currently investigating whether the phenotype observed is due to a Y chromosome mutation or an epistatic interaction with other genes. This work was supported by the National Institutes of Health Research Grant AI46709.