PRECURSOR CELLS TO CD3-INTERMEDIATE (CD3(INT)) LIVER MONONUCLEAR-CELLS IN THE ADULT LIVER - FURTHER EVIDENCE FOR THE EXTRATHYMIC DEVELOPMENT OF CD3(INT) LIVER MONONUCLEAR-CELLS

Liver mononuclear cells (LMNC) can be divided into CD3-high positive ( CD3(hi)), CD3-intermediate positive (CD3(int)) and CD3(-) populations. CD3(int) LMNC, but not CD3(hi) LMNC, are considered to be extrathymic ally derived because they are found in the liver of nude mice and adul t thymectomized lethally irradiated bone marrow chimeras. CD3(int) LMN C express NK1.1 and show a skewed T cell receptor (TCR) V region reper toire with relatively high levels of V beta 8 and V alpha 14 expressio n, further suggesting that they belong to a different lineage from con ventional T cells, which lack NK1.1 expression and V region skewing. S ince the liver has been proposed to be a site of extrathymic T cell di fferentiation in adult mice, we analyzed LMNC for the presence of T ce ll precursors. CD3(-) LMNC contained CD4(-)CD8(-) cells and CD4(lo)CD8 (-) cells. Reverse transcription-polymerase chain reaction analysis sh owed both CD3(-) populations express the recombination-activating gene -1, which is indispensable in gene rearrangement of TCR and expressed by thymic T cell precursors. Furthermore, when electronically sorted CD3(-) LMNC were cultured in medium without any feeder cells or exogen ously added cytokines for 24 h, CD3(int) cells, but not CD3(hi) cells, appeared. These results suggest that the adult liver contains T cell precursors that lack the expression of the CD3/TCR complex, but are st rongly committed to differentiate into extrathymic liver CD3(int) T ce lls.