Syngeneic preference manifested by thymic stroma during development of thymocytes from bone marrow cells

Abstract

The question whether major histocompatibility complex (MHC) recognition is expressed in interactions between thymocyte progenitors and thymic stroma cells was investigated in an organ culture system, in which inductive interactions between thymic stroma cells and thymocyte progenitors of different MHC haplotypes could be measured. Thymocyte-depleted fetal thymuses were reconstituted with mixtures of syngeneic and allogeneic bone marrow cells, which also differed in their Thy-1 allele. The relative repopulating ability of the cells was estimated by determining the percentage of emerging Thy-1.1+ vs. Thy-1.2+ thymocytes. Similar values of Thy-1+ cells of the bone marrow donor type developed when the thymus were reconstituted by bone marrow from donors which were either syngeneic or allogeneic to the thymic explants. However, when a 1:1 mixture of syngeneic and allogeneic cells was applied to the thymus, a syngeneic preference was manifested in development of Thy-1+ cells. When mixtures of bone marrow cells from C57BL/Ka (Thy-1.1) and B10.A MHC-congenic (Thy-1.2) mice were used, this developmental preference was found to map to the I-E region. Thymocytes derived from bone marrow cells allogeneic to the stroma, seeded on their own, manifested an advantage over allogeneic bone marrow cells from a different MHC haplotype, in a secondary reconstitution. This suggested that allogeneic bone marrow progenitor cells can be "educated" by the host thymic stroma to behave, in the competitive reconstitution, like syngeneic cells.

MHC‐Linked Syngeneic Developmental Preference inThymic Lobes Colonized with Bone Marrow Cells: A Mathematical model

“…For these reasons, the role of major histocompatibility complex (MHC) molecules in thymocyte development has been studied extensively (yon Boehmer, 1991;yon Kisielow and von Blackman et al, 1990). Recent experimental studies (Eren et al, 1989;Sharp et al, 1991Sharp et al, , 1995Fridkis-Hareli et al, 1993) suggest that, in addition to their role in selection processes, which occur relatively late in thymocyte development (in the late double positive and single positive stages), MHC molecules may also play a role in the very early *Corresponding author. Tel."…”

“…Allogeneic BM cells on their own were found to be capable of reconstituting the FT to similar levels as syngeneic BM cells. However, when allogeneic BM cells were mixed (at a 1:1 ratio) with syngeneic BM cells, a developmental preference of the syngeneic BM cells was observed: More than 80% of the developing thymocytes originated from the syngeneic BM (Eren et al, 1989;Sharp et al, 1991). Genetic mapping experiments (Eren et al, 1989) suggested that the MHC class II (I-E and I-A) region may be important in determining SDP; hence, we refer to this phenomenon as " MHC-linked.…”

“…However, when allogeneic BM cells were mixed (at a 1:1 ratio) with syngeneic BM cells, a developmental preference of the syngeneic BM cells was observed: More than 80% of the developing thymocytes originated from the syngeneic BM (Eren et al, 1989;Sharp et al, 1991). Genetic mapping experiments (Eren et al, 1989) suggested that the MHC class II (I-E and I-A) region may be important in determining SDP; hence, we refer to this phenomenon as " MHC-linked. " Experiments of sequential seeding, in which BM cells from one source were seeded first, and 24 hr later cells from another source were added to the culture and incubated for two additional days, show that the major impact of MHC-linked competition was related to events occurring in the first 24 hr of seeding (Sharp et al., 1991)--an earlier stage than previously described for the involvement of MHC molecules in selection processes in the thymus.…”

“…First, the behavior of cells in this compartment is indeed different from that of later thymocytes: They compete not on all thymic resources, but on specific "seeding niches," the number of which is limited (=100) Mehr et al, 1994). Second (c) We assume that cells of all compartments except the newly seeded cell compartment compete for space and resources within the thymus (Metcalf, 1963 (Eren et al, 1989;Sharp et al, 1991Sharp et al, , 1995. Cells were seeded on the FT, as described in the text, and then the FT were cultured for 11 days, after which the resulting thymocytes were harvested.…”

“…When PBL were used, they were In contrast to this prediction, in the experiments, the results are not symmetric, unless there are no mature T cells present. Table I shows the range of values from several experiments (Eren et al, 1989;Sharp et al, 1995). Unseparated BM, which contain up to 10% mature T cells, were seeded in all three protocols (Table I, (Eren et al, 1990;Mehr et al, 1993Mehr et al, , 1994.…”