VIH : nouvelle vision du renouvellement des lymphocytes T CD4+.
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Des etudes portant exclusivement sur le sang peripherique ont permis la formulation d' une theorie selon laquelle l' intensite de la replication virale et les effets cytopathiques qui y sont associes forceraient le systeme immunitaire a renouveler rapidement les lymphocytes T CD4+. Cela conduirait ineluctablement a l' epuisement du systeme immunitaire. Cette theorie est desormais contredite par de nouvelles donnees experimentales tenant compte cette fois non seulement du sang peripherique, mais aussi du renouvellement des lymphocytes T au sein des ganglions lymphatiques. En effet, des mesures directes et indirectes du taux de renouvellement lymphocytaire indiquent que le VIH semblerait plutot interferer avec la regeneration des lymphocytes T CD4+. Ainsi, cette reduction de l' apport quotidien en nouveaux lymphocytes T CD4+, combinee a la destruction cellulaire causee par le virus, ferait en sorte que le nombre total de lymphocytes T CD4+ ne puisse que decroitre au cours de l' evolution fatidique de l' infection.The initial idea that high amounts of cytopathic virus produced everyday can drive high CD4+ T cell production seemed logical and explained the progressive CD4+ T cell depletion observed in HIV-infected subjects. It was hypothesized that the CD4+ T lymphocyte production was increased up to 70-fold in HIV-infected subjects. Determination of the CD4+ T cell production was based on the kinetics of CD4+ T cell recovery following initiation of highly-active antiretroviral therapy (HAART). However, this analysis was limited by: (1) the assumption that blood CD4+ T cells are representative of the lymph node T cells; and (2) the lack of estimates of CD4+ T lymphocyte turnover in healthy HIV-negative subjects. Several immunologists have expressed caution regarding the assumptions used in modeling CD4+ T cell dynamics. Recent findings clearly show that blood is not representative of lymphoid tissues. Indeed, when blood and lymph node compartments are considered together, we find that HIV -infected subjects naive to antiretroviral treatment have similar or lower CD4+ T cell production, as compared to healthy subjects. This observation suggests an impaired T cell renewal capacity in HIV-1 infected patients. Furthermore, the initial rise observed in blood CD4+ T cells of patients under HAART might not necessarily reflect newly formed CD4+ T cells. Indeed, the rapid increase in CD4+ T cells in the blood observed shortly after initiation of HAART is caused by T cell redistribution from peripheral tissues to blood and not T cell proliferation. In addition, immunophenotyping shows that the T cell increases during early HAART therapy are restricted to memory populations. In contrast, the naive T cell population does not immediately respond to HAART, their numbers in blood increase only after weeks of therapy. Based on those results, there is no evidence for an increased CD4+ T cell production in HIV-infected subjects and therefore, CD4+ T cell depletion cannot be explain ed by exhaustion of T cell renewal due to virus-induced cell destruction. After initiation of HAART, naive CD4+ T cell number slowly increases over a six month period followed by a stabilization. The mechanism of renewal of CD4+ T cells is, thus, still intact in HIV-infected subjects in the early stages of the disease and therapy may indeed allow for T cell reconstitution.
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Fleury, S - Soudeyns, H - Pantaleo, G, VIH : nouvelle vision du renouvellement des lymphocytes T CD4+., Med Sci (Paris), 1999, Vol. 15, N° 8-9; p.958-65