6th Conference on Retroviruses and Opportunistic Infections
Chicago, IL - January 31-February 4, 1999
Direct evidence for de novo T cell generation in adults is provided by the presence of T cell receptor DNA excision circles in peripheral blood lymphocytes.
Poulin JF, Viswanathan MN, Komanduri KV, Wieder E, Ringuette N, Brizard F, Harris J, Bourbonniere M, McCune JM, Sekaly RP; McGill University, Montreal, Quebec, Canada.
De novo T cell production is thought to occur in human although its magnitude, its diversity and its features are not clearly understood. Some have postulated that de novo T cell output remains stable and its decrease is due to the continuous challenge of T cells by antigens. Others argue that the intrinsic function of the thymus and is negligible after puberty. We propose here a novel and non-invasive assay that has allowed us to monitor de novo T cell generation through the quantitation of the frequency of the DNA excision circles issued from a distinct TCRb V-DJ segments recombination. We show here that de novo T cell production occurs throughout childhood and adult life in humans and its magnitude is very much age dependent. We also demonstrate the multiple TCR Vbusage of recently rearranged T cells. Moreover, our study demonstrates that CD4-expressing T cells who have recently undergone TCR rearrangement are not exclusive to the CD45RA+ compartment but can be found in a subset of CD45RO+ cells. Detection of several distinct DNA excision circles provide new insights in the quantitation of one's ability to produce new T cell clones and to generate a broad repertoire, an important caracteristic to define in order to evaluate the immune reconstitution potential of an individual.
Keywords: AEGIS, Receptors, Antigen, T-Cell, T-Lymphocytes, Thymus Gland, Antigens, CD45, Diethylstilbestrol, Antigens, CD4, Resin Cements, DNA, Clone Cells, Direct, Adult, Human, AIDS
