The development and maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) requires the balanced reconstitution of donor-derived @entity404 regulatory T cells (CD4Tregs) as well as effector @entity404 (conventional @entity404 T cells [CD4Tcons]) and @entity405 T cells. To characterize the complex mechanisms that lead to unbalanced recovery of these distinct T-cell populations, we studied 107 adult @entity1 who received T-replete stem cell grafts after reduced-intensity conditioning. Immune reconstitution of CD4Treg, CD4Tcon, and @entity405 T cells was monitored for a 2-year period. CD3 T-cell counts gradually recovered to normal levels during this period but @entity405 T cells recovered more rapidly than either CD4Tregs or CD4Tcons. Reconstituting @entity404 Tregs and CD4Tcons were predominantly central memory (CM) and effector memory (EM) cells and @entity405 T cells were predominantly terminal EM cells. Thymic generation of naive @entity404 Tcon and @entity405 T cells was maintained but thymic production of @entity404 Tregs was markedly decreased with little recovery during the 2-year study. T-cell proliferation was skewed in favor of CM and EM @entity404 Tcon and @entity405 T cells, especially 6 to 12 months after HSCT. Intracellular expression of @entity588 was increased in CD4Tcon and @entity405 T cells in the first 3 to 6 months after HSCT. Early recovery of naive and CM fractions within each T-cell population 3 months after transplant was also strongly correlated with the subsequent development of @entity2132 ( @entity2132 ). These dynamic imbalances favor the production, expansion, and persistence of effector T cells over @entity404 Tregs and were associated with the development of chronic @entity2132 .

Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity588 :: ('596', 'Gene') :: ['BCL2'] @entity2132 :: ('MESH:D006086', 'Disease') :: ['GVHD', 'chronic graft-versus-host disease'] @entity405 :: ('925', 'Gene') :: ['CD8']
@entity2132 :: (MESH:D006086,Disease) :: ['GVHD']
