AN ALLOGENEIC MICROENVIRONMENT INFLUENCES THE PHENOTYPE OF INTERMEDIATE T-CELL RECEPTOR-CELLS EXPANDING IN MRL-LPR LPR MICE/

MRL-lpr/lpr (lpr) mice fall victim to autoimmune disease owing to a ly mphoproliferative disorder mainly of double-negative (DN) CD4(-) CD8(- ) alpha beta T cells expressing a low density of interleukin-2 recepto r beta-chain (IL-2R beta). It was previously revealed that the lpr gen e is a defective Fas gene, into which an early transposon (ETn) of ret rovirus is transfected. As a result of the failure of apoptosis, inter mediate T-cell receptor (TCR) cells (i.e. TCRint cells) with DN phenot ype abnormally accumulate in the periphery of lpr mice. We investigate d herein how these TCRint cells are selected in terms of CD4, CD8 and TCR in lpr mice. When a whole fraction of mononuclear cells (MNC) in v arious immune organs of lpr mice was injected into scid mice (allogene ic circumstance), CD8(+) TCRint cells mainly expanded. They had a high density of IL-2R beta. This was true when bone marrow cells of lpr mi ce were injected into scid mice. On the other hand, when MNC of the sp leen and bone marrow in lpr mice were injected into irradiated (9 Gy) lpr mice (syngeneic circumstance), the major expanding cells were DN T CRint cells expressing a low density of IL-2R beta. A cell-sorting exp eriment for purified fractions demonstrated that only CD8(+) cells rec onstituted TCRint cells in scid mice. Namely, DN CD4(-) CD8(-) cells a s well as CD4(+) cells which once acquired the mature phenotype, no lo nger switched their phenotype. These results suggest that the phenotyp e of TCRint cells is influenced by the surrounding microenvironment.