CD4+ T-CELLS THAT EXPRESS HIGH-LEVELS OF CD45RB INDUCE WASTING DISEASE WHEN TRANSFERRED INTO CONGENIC SEVERE COMBINED IMMUNODEFICIENT MICE - DISEASE DEVELOPMENT IS PREVENTED BY COTRANSFER OF PURIFIED CD4+ T-CELLS

Purified CD4+ lymph node T cells were sorted into two populations on the basis of their expression of CD45RB (CD45RB(hi) and CD45RB(lo)) and injected into congenic severe combined immunodeficient (SCID) mice. After a period of time that was dependent on the number of cells injected, the SCID mice that received CD45RB(hi)/CD4+ T cells developed a wasting disease that was not seen in SCID mice that received the CD4+/CD45RB(lo) cells or whole lymph node cells. At death, SCID mice that received the CD4+/CD45RB(hi) cells had increased spleen and lymph node cellularity compared with normal SCID mice and SCID mice that received the CD4+/CD45RB(lo)T cells. The spleen and lymph node contained CD4+ cells and neither CD8+ nor surface immunoglobulin M-positive cells, plus a population of cells that did not express any of those markers. At necropsy, the SCID mice that received the CD4+/CD45RB(hi) cells had significant hyperplasia of the intestinal mucosa with significant lymphoid cell accumulation in the lamina propria. Interestingly, mice that received mixtures of whole lymph node or purified CD4+ cells with CD4+/CD45RB(hi) cells did not develop weight loss, indicating that the unseparated CD4+ population contained cells that were capable of regulating the reactivity of the CD4+/CD45RB(hi) cells.