Developmental heterogeneity of V gamma 1.1 T cells in the mouse liver.

Modifications at V-(D)-J junctions increase the diversity of T-cell receptors (TCR). It has been shown that the levels of N-nucleotide insertion at the V-(D)-J junction in TCR transcripts are different between fetal and adult stages. To clarify developmental stages and pathways of gamma delta T cells in the liver, we analysed the nucleotide sequence of V gamma 1.1-J gamma 4 junctions of intra-hepatic lymphocytes (IHL), spleen cells and developing thymocytes from normal and athymic nude mice. The level of N-insertion increased in thymocytes during ontogeny. The percentage of V gamma 1.1-J gamma 4 transcripts with N-insertion was 3% at day 16 of gestation, 42% at newborn, and 89% at 7 weeks. Transcripts from normal IHL showed intermediate levels of N-insertion between those of newborn and adult thymocytes. In contrast the percentage of N-insertion in nude IHL was 47%, and this value was comparable to that of newborn thymocytes. Among the transcripts of normal IHL, the sequences common with nude IHL showed a newborn level of N-insertion (38%), and the remaining sequences showed an adult level (89%). These results suggested the possibility that V gamma 1.1-expressing T cells in IHL might be a heterogeneous population consisting of the cells developed extrathymically as well as the cells developed intrathymically. The V gamma 1.1-J gamma 4 junctions from spleen cells showed less variability than those from IHL and adult thymocytes. It suggested that gamma delta T cells bearing specific V gamma 1.1 TCR develop and/or home in the spleen.