First Author | Capone M | Year | 1995 |
Journal | J Immunol | Volume | 154 |
Issue | 10 | Pages | 5165-72 |
PubMed ID | 7730622 | Mgi Jnum | J:25113 |
Mgi Id | MGI:72826 | Doi | 10.4049/jimmunol.154.10.5165 |
Citation | Capone M, et al. (1995) T cell development in TCR-alpha beta transgenic mice. Analysis using V(D)J recombination substrates. J Immunol 154(10):5165-72 |
abstractText | The major pathway of intrathymic T cell differentiation leads CD4-8- (DN) T lineage-committed precursors to TCR-alpha beta+ CD4+8- or CD4-84+ (SP) T lymphocytes. The expression of functionally rearranged TCR-alpha beta transgenes (Tg-TCR) may influence thymocyte development by affecting the various selection events that control T cell differentiation. To gain insights into these processes, we have produced double transgenic animals carrying V(D)J recombination substrates in addition to the MHC class I (H-2Kb) allospecific KB5C20 Tg-TCR. We have analyzed substrate rearrangements in purified populations of Tg-TCR+ thymocytes in the situation of positive or negative selection. The profile of rearrangements found in SP thymocytes, positively selected for the Tg-TCR, suggests that expression of the KB5C20 Tg-TCR has only a minimal influence on substrate V(D)J recombination in cells differentiating along the major alpha beta T cell developmental pathway. In contrast, Tg-TCR+ DN thymocytes, in both positively and negatively selecting haplotypes, presented a profile that implies premature cessation of substrate rearrangements. This profile was maintained in peripheral Tg-TCR+ DN cells and was distinct from the one found in CD25+, alpha beta+, or gamma delta+ DN cells purified from mice transgenic for the recombination substrates only. These results are discussed with respect to the possible origin and differentiation pathway of Tg-TCR+ DN and SP cells. |