Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques.

Background: Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques.

Results: The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% +/- 4%.

DNA repair and the immune system: From V(D)J recombination to aging lymphocytes.

B and T lymphocytes are exposed to various genotoxic stresses during their life, which originate from programmed molecular mechanisms during their development and maturation or are secondary to cellular metabolism during acute phases of cell proliferation and activation during immune responses. How lymphocytes handle these multiple genomic assault has become a focus of interest over the years, perhaps beginning with the identification of the murine scid model in the early 80s when it was recognized that DNA repair deficiencies had profound consequences on the immune system. In this respect, the immune system represents an ideal model to study DNA damage responses (DDR) and the survey of immune deficiency conditions in humans or the development of specific animal models provided many major contributions in our understanding of the various biochemical pathways at play during DDR in general.

Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques.

Experimental infection of macaques with pathogenic strains of simian immunodeficiency virus (SIV) represents one of the most relevant animal models for studying HIV pathogenesis. In this study, we demonstrated a significant decrease in the generation of CD4+ T cells from bone marrow (BM) CD34+ progenitors in macaques infected with SIVmac251. This decrease appears to result from changes in the clonogenic potential of BM progenitors of both the myeloid and lymphoid lineages.