Intrathymic proliferation of perinatal mouse alpha beta and gamma delta T cell receptor-expressing mature T cells.

Using three colour flow microfluorimetry to analyse simultaneously two cell surface molecules and DNA content, CD4 SP cells in the late foetal and early postnatal thymus were found to contain significant numbers of cells in the S and G2 + M phases of the cell cycle. In contrast to neonatal thymocytes, CD4 SP cells in the adult thymus were found to be non-cycling. Two other phenotypic properties, namely expression of J11d and larger cell size, also distinguish perinatal from adult CD4 SP cells. In the perinatal thymus of (B/6 x D2)F1 mice, CD4 SP thymocytes expressing either V beta 6 (Mls-reactive) or V beta 11 (I-E-reactive) TCR are deleted by negative selection yet cell cycle analysis showed that, coincident with deletion, they were cycling. Thus negative selection in the perinatal thymus was operating on a population of cycling cells. Finally, perinatal CD3+, gamma delta TCR-expressing DN thymocytes were also found to be cycling. Taken together, these results show that, prior to migration to peripheral lymphoid tissues, in the perinatal period there is intrathymic proliferation of developing gamma delta- and alpha beta-expressing T cells.