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In vivo dynamics of CD4 – 8 – thymocytes. Proliferation, renewal and differentiation of different cell subsets studied by DNA biosynthetic labeling and surface antigen detection
Author(s) -
Penit Claude,
Vasseur Florence,
Papiernik Martne
Publication year - 1988
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830180907
Subject(s) - biology , in vivo , microbiology and biotechnology , cellular differentiation , dynamics (music) , dna , antigen , cell growth , immunology , genetics , gene , physics , acoustics
Abstract The proliferative status of CD4 − 8 − thymocyte subsets was determined by in vivo or in vitro labeling with bromodeoxyuridine (BrdUrd), a nonreutilized thymidine analogue detectable with a monoclonal antibody, simultaneously with relevant surface proteins. An actively cycling subset [J11d, interleukin 2 receptor‐positive (IL2R)] was defined, besides a relatively resting one (J11d‐, Pgpl, T cell receptor‐positive). Continuous per os administration of BrdUrd showed that 85% only of CD4 − 8 − thymocytes were labeled in 6 days confirming the existence of a relatively long‐term resting subset. By contrast, CD48 thymocytes were all labeled in 3–4 days. Observation of labeled CD4 − 8 − cells after pulse labeling showed an immediate decrease of their absolute number per thymus, confirming their low autorenewal capacity. However, a small number of labeled cells which were hydroxyurea or colchicine resistant remained CD4 − 8 − for several days and progressively acquired surface expression of IL2R. IL2R expression by cycling CD4 − 8 − cells during thymus regeneration after antimitogenic drug treatment was rapid, but very transient. According to these results most CD4 − 8 − thymocytes appear as largely engaged in a proliferation‐dependent differentiative process, and do not behave as true stem cells. Consequently, this subset is principally renewed by thymic immigration of exogenously produced resting cells. However, a tenfold expansion of CD4 − 8 − cells was found in the fetal and regenerating thymus, suggesting two proliferative phases during intrathymic CD4 − 8 − cell maturation, the first one yielding to cell expansion and the second to cell differentiation. A tentative evaluation of daily cell immigration is proposed starting with the determination of the number of cells beginning DNA synthesis each day. A global model is finally discussed by confronting our kinetic results with the known reconstitution capacities of CD4 − 8 − thymocyte subsets.