The developing human immune system: T-cell receptor repertoire of childrenand young adults shows a wide discrepancy in the frequency of persistent oligoclonal T-cell expansions

While the T-cell receptor (TCR) repertoire of the newborn is highly diverse , a gradual alteration in diversity of the expressed TCR repertoire, in par ticular the oligoclonality of CD8(+) T cells, occurs with increasing age. T he timing of the initiation of this process is unknown. These changes are a ssociated with an accumulation of T-cell expansions, thought to be in respo nse to chronic antigen stimulation, frequently by persistent viruses such a s Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Using reverse transcr iption-polymerase chain reaction heteroduplex analysis we have characterize d the TCR expression of CD4 and CD8 cells from healthy young children and a dults in order to delineate the age range at which these oligoclonal popula tions appear. We demonstrate that considerable oligoclonality can occur, ev en in healthy young children, and also that these expanded clonotypes persi st. These are shown by heteroduplex to be exclusively within the CD28(-) su bpopulation. The presence of such oligoclonal expansions correlates closely with the percentage of CD8(+) cells that have the CD28 phenotype. However, we also show that control of chronic infection with EBV or CMV may coexist with a highly diverse, polyclonal TCR repertoire well into adulthood. Thes e studies suggest that many factors affect the overall regulation of clone size in response to chronic antigens during the development of the immune s ystem.