CD4(+) CD45RB low-density cells from untreated mice prevent acute allograft rejection

In the absence of therapy that suppresses the action of the immune system, the immune response to transplantation Ags results in rapid rejection of th e transplant. The most successful mechanism so far described that achieves organ-specific immunological tolerance is that which controls peripheral to lerance to self-tissue. Until now, no similarities have been documented bet ween the peripheral response to self-rigs and the response to transplantati on Ags, CD4(+) cells that express a high density of CD45RB (in the mouse) a nd CD45RC (in the rat) on their surface have been shown to cause a number o f autoimmune disorders. In contrast, autoimmunity caused by the CD45RB high -density cells is inhibited by CD4(+) CD45RB cells that express a low densi ty of CD45RB (CD45RC in the rat). In this paper we show that CD4(+) CD45RB high-density cells are sufficient to cause rejection of a MHC-mismatched pa ncreas allograft, whereas CD4(+) CD45RB low-density cells are not. Unexpect edly, the CD45RB low-density cells prevent the CD45RB(high) expressing cell s from causing rejection. These data suggest that the response to foreign t issue can be controlled in the same way as the response to self-tissue.