The developing human immune system: T-cell receptor repertoire of children and 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 particular the oligoclonality of CD8+ T cells, occurs with increasing age. The timing of the initiation of this process is unknown. These changes are associated with an accumulation of T-cell expansions, thought to be in response to chronic antigen stimulation, frequently by persistent viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Using reverse transcription-polymerase chain reaction heteroduplex analysis we have characterized the TCR expression of CD4 and CD8 cells from healthy young children and adults in order to delineate the age range at which these oligoclonal populations appear. We demonstrate that considerable oligoclonality can occur, even in healthy young children, and also that these expanded clonotypes persist. These are shown by heteroduplex to be exclusively within the CD28- subpopulation. 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. These studies suggest that many factors affect the overall regulation of clone size in response to chronic antigens during the development of the immune system.
Wedderburn
L R
LR
Department of Molecular Pathology, University College London, UK. L.Wedderburn@ich.ucl.ac.uk
Patel
A
A
Varsani
H
H
Woo
P
P
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D002999:Clone Cells / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell