Abstract
Understanding cell dynamics in animal models have implications for therapeutic strategies elaborated against leukemia in human. Quantification of the cell turnover in closely related primate systems is particularly important for rare and aggressive forms of human cancers, such as adult T-cell leukemia. For this purpose, we have measured the death and proliferation rates of the CD4+ T lymphocyte population in squirrel monkeys (Saimiri sciureus) infected by human T-lymphotropic virus type 1 (HTLV-1). The kinetics of in vivo bromodeoxyuridine labeling revealed no modulation of the cell turnover in HTLV-1-infected monkeys with normal CD4 cell counts. In contrast, a substantial decrease in the proliferation rate of the CD4+ T population was observed in lymphocytic monkeys (e.g. characterized by excessive proportions of CD4+ T lymphocytes and by the presence of abnormal flower-like cells). Unexpectedly, onset of HTLV-associated leukemia thus occurs in the absence of increased CD4+ T-cell proliferation. This dynamics significantly differs from the generalized activation of the T-cell turnover induced by other primate lymphotropic viruses like HIV and SIV.
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Acknowledgements
We thank the ‘Belgian Foundation against Cancer’, the Télévie, the ‘Fortis Bank Assurance’, the ‘FNRS’, the ‘Loterie Nationale’, the ‘Pôles d’attraction interuniversitaires pour le compte de l'Etat belge, Services fédéraux des affaires scientifiques, techniques et culturelles’, the ‘Actions de Recherche Concertées du Ministère de la Communauté Française’, the ‘Bourse de voyage du ministère de la Communauté Française de Belgique’, and the ‘Wellcome Trust’ for financial support. RK and LW are research directors of the ‘Fonds National de la Recherche Scientifique’ (FNRS), whereas CD is a postdoctoral researcher (FNRS). Part of this study was supported by the French Ministry of Research ‘Programme de Recherche fondamentale en Microbiologie des Maladies Infectieuses et Parasitaires’ and the Association pour la Recherche contre le Cancer (ARC-Grant no. 7590 and no. 5700 to MK). JMH is a fellow of the ‘Fondation pour la Recherche Medicale’ (FRM), the ‘Région Guyane’ and the ‘Institut Pasteur’. We are grateful to Karen Willard-Gallo (Bordet ULB, Brussels) and Pierre Kerkhofs (CERVA, Brussels) for laboratory facilities, and Mathieu Boxus (FUSAG, Gembloux), Hugues Duvillier (Bordet ULB, Brussels), and Patrice Urbain (FUSAG, Gembloux) for their experimental help.
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Debacq, C., Héraud, JM., Asquith, B. et al. Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic virus type 1. Oncogene 24, 7514–7523 (2005). https://doi.org/10.1038/sj.onc.1208896
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DOI: https://doi.org/10.1038/sj.onc.1208896
