Masters Theses

Date of Award

8-1992

Degree Type

Thesis

Degree Name

Master of Science

Major Professor

Virginia L. Godfrey

Abstract

The scurfy (sj) mutation is X-linked recessive and results in an autoimmune lymphoproliferative disease with lesions resembling those characteristic of Graft vs Host Disease (GVDH). Like GVDH, the scurfy disease is T cell mediated. Because other genetically determined murine autoimmune diseases, such as those caused by lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld), result in a disproportionate population of abnormal T cells, lymphoid cells of the scurfy mouse and age-matched normal males were analyzed and compared by flow cytometric techniques. Scurfy (Xsf/Y) and scurfy sparse-fur (Xsf spf/Y) splenic cells had fewer B220+ B cells than normal splenic cells. This result was due to a large proportion of Xsf/Y or Xsf spf/Y B cells having terminally differentiated into plasma cells which do not express B220. The Xsf/Y lymph nodes had fewer T helper, CD4+, cells than normal. This reduction in CD4+ cells, similar to that found in HIV+ AIDS patients, is possibly a result of T cytotoxic, CD8+, cells lysing CD4+ cells. There was an increase in Xsf/Y CD4+ and CD8+ cells in the thymus with a simultaneous decrease in CD4+CD8+ cells which is probably due to cortisone-mediated depletion. Flow cytometric analysis of 4 day old Xsf spf/Y and normal thymocytes revealed the same increase in CD4+ and CD8+ cells and the same decrease in CD4+CD8+ cells. However, this was not due to cortisone depeletion because at 8 days the Xsf spf/Y thymuses were histologically normal and did not have a reduction in CD4+CD8+ cells, even though there was a slight increase in the CD4+ and CD8+ cells. These data suggest that there may be a defect in a portion of the negative selection of T cells in the scurfy thumus.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS