Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for XXXX .

@entity1 @entity8 @entity19 @entity1778 @entity2132 @entity465 @entity1583 @entity2280
UNASSIGNED: Persistent complete donor chimerism is an important clinical indicator for remissions of @entity1583 after HLA-matched allogeneic @entity8 ( @entity8 ). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus- @entity1778 effects and @entity2132 suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic @entity8 . Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 @entity1 after allogeneic HLA-matched, HA-1 mismatched @entity8 . Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 @entity1 lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type @entity2280 + cells with HA-1 CTLs isolated after allogeneic @entity8 prevented progenitor and cobblestone area forming cell growth in vitro and @entity1 hematopoietic engraftment in @entity465 @entity19 . Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic @entity8 to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more @entity1 are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and @entity1778 remission after allogeneic @entity8 .
