Molecular and cellular basis of T cell lineage commitment.

The thymus forms as an alymphoid thymic primordium with T cell differentiation requiring the seeding of this anlage. This review will focus on the characteristics of the hematopoietic progenitors which colonize the thymus and their subsequent commitment/differentiation, both in mice and men. Within the thymus, the interplay between Notch1 and IL-7 signals is crucial for the orchestration of T cell development, but the precise requirements for these factors in murine and human thympoeisis are not synonymous. Recent advances in our understanding of the mechanisms regulating precursor entry and their maintenance in the thymus will also be presented.

Molecular identity of skin and blood T-cell clones in cutaneous T-cell lymphoma patients as determined from the migration pattern of the T-cell receptor-gamma gene by capillary electrophoresis.

The presence of a dominant clonal T-cell population in skin lesions is an important clue in the diagnosis of cutaneous T-cell lymphoma (CTCL). However, it has never been determined whether dominant T-cell receptor (TCR) rearrangements identified in skin lesions and blood from CTCL patients, displaying strictly identical migration patterns by capillary electrophoresis, actually correspond to identical clones. As this information has potential clinical relevance, TCR-gamma (TCRG) gene-derived amplified fragments from dominant blood and skin T-cell clones featuring either identical or slightly different capillary electrophoresis migration patterns were analyzed in eleven CTCL patients. In nine patients with identical electrophoretic migration patterns, sequence analyses revealed the dominant skin and blood T-cell clones to be identical. In contrast, in two patients displaying slight migration differences between skin and blood samples, the TCRG sequences were distinct. Additionally, capillary electrophoresis appears more sensitive and accurate than heteroduplex analysis and in silico analysis of samples of different origins is possible a posteriori. These results demonstrate the efficacy of capillary electrophoresis in assessing molecular identity and discrepancy of dominant T-cell populations obtained from different tissues or at different times, facilitating diagnosis and follow-up.