Thymus-independent expansion of T lymphocytes in children after allogeneic bone marrow transplantation

The contribution of the thymus-dependent pathway and thymus-independent pathways for T cell regeneration after BRIT in children is still unclear. We analyzed the kinetics of T cell regenerative pathways after allogeneic BRIT. The number of CD4(+)CD45RA(+) T cells, a thymus-dependent population, was very low until 3 months after BRIT. The numbers of CD28(-) T cells and CD8(+) T cells expressing CD8 alpha/alpha homodimer (CD8 alpha/alpha(+) T cells), a thymus-independent population, increased shortly after BRIT, beyond the levels of healthy children in some patients. The numbers of V gamma 9(+)V delta 2(+) and V alpha 24(+) T cells, which represent populations of extrathymic development, were less than 200/mu l during the 6 months after BRIT. There was a significant inverse correlation between the percentages of CD4(+)CD45RA(+) and CD28(-) T cells at 1 month, and a positive correlation between the percentages of CD28(-) and CD8 alpha/alpha(+) T cells at 2 and 3 months after BRIT. The mean age at BRIT was higher in patients with a high level of CD8 alpha/alpha(+) T cells than in those without an increase in these cells, suggesting the influence of thymic function on the regenerative pathways. These results suggest that the thymus-independent pathway is the dominant source of T cells even in children shortly after allogeneic BMT.