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Targeted complementation of MHC class II deficiency by intrathymic delivery of recombinant adenoviruses
R Rooke1, C Waltzinger, C Benoist
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et la Recherche Médicale, Université Louis Pasteur, Illkirch, Strasbourg, France.
De novo differentiation of CD4+ T cells was provoked in mice lacking major histocompatibility complex (MHC) class II molecules by intrathymic injection of adenovirus vectors carrying class II genes. This permits a new approach to questions concerning the dynamics of CD4+ T cell compartments in the thymus and peripheral lymphoid organs. Here two issues are explored. First, we show that mature CD4+ CD8- cells reside in the thymus for a protracted period before emigrating to the periphery, highlighting the potential importance of, and our ignorance of, the postselection maturation period. Second, we demonstrate that the survival of CD4+ cells in peripheral lymphoid organs is markedly curtailed when class II molecules are absent and is not further reduced in the absence of both class II and class I molecules, raising the possibility that MHC-mediated selection may continue in the periphery.
De novo differentiation of CD4+ T cells was provoked in mice lacking major histocompatibility complex (MHC) class II molecules by intrathymic injection of adenovirus vectors carrying class II genes. This permits a new approach to questions concerning the dynamics of CD4+ T cell compartments in the thymus and peripheral lymphoid organs. Here two issues are explored. First, we show that mature CD4+ CD8- cells reside in the thymus for a protracted period before emigrating to the periphery, highlighting the potential importance of, and our ignorance of, the postselection maturation period. Second, we demonstrate that the survival of CD4+ cells in peripheral lymphoid organs is markedly curtailed when class II molecules are absent and is not further reduced in the absence of both class II and class I molecules, raising the possibility that MHC-mediated selection may continue in the periphery.