Flow cytometric analysis of lymphoid cells of the scurfy mouse

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 (X^sf/Y) and scurfy sparse-fur (X^{sf spf}/Y) splenic cells had fewer B220⁺ B cells than normal splenic cells. This result was due to a large proportion of X^sf/Y or X^{sf spf}/Y B cells having terminally differentiated into plasma cells which do not express B220. The X^sf/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 X^sf/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 X^{sf 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 X^{sf 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.