Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets

Early in life, thymic export establishes the size and the diversity of the human naive T-cell pool. Yet, on puberty thymic activity drastically decreases. Because the overall size of the naive T-cell pool decreases only marginally during ageing, peripheral postthymic expansion of naive T cells has been postulated to account partly for the maintenance of T-cell immunity in adults. So far, the analysis of these processes had been hampered by the inability to distinguish recent thymic emigrants from proliferated, peripheral, naive T cells. However, recently, CD31 has been introduced as a marker to distinguish 2 subsets of naive CD4(+) T cells with distinct T-cell receptor excision circle (TREC) content in the peripheral blood of healthy humans. Here, we review studies that have characterized TREC(hi) CD31(+ thymic)naive CD4(+) T cells and have accordingly used the assessment of this distinct subset of naive CD4(+) T cells as a correlate of thymic activity. We will discuss further potential clinical applications and how more research on CD31(+ thymic)naive and CD31(- central)naive CD4(+) T cells may foster our knowledge of the impact of thymic involution on immune competence.