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Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107
Graft-vs-host disease (GVHD) is a major complication of allogeneic
bone marrow transplantation. Experimentally, lethal GVHD can be induced
in MHC-matched strain combinations differing in expression of multiple
minor histocompatibility Ags (miHA). Recently, the GVHD potential of
C57BL/6By (B6) T cells in irradiated BALB.B (both
H2b) and related CXB recombinant inbred strains of
mice has been studied to determine the scope of the response to miHA in
vivo and how it compared with CTL responses to immunodominant miHA in
vitro. The GVHD response in these strain combinations appeared to be
limited to a few Ags, yet there was no correlation of these miHA with
that of in vitro CTL responses. To further investigate the role of
CD8+ T cells in GVHD, we analyzed positively selected
miHA-specific donor CD8+ thoracic duct lymphocytes (TDL)
collected from irradiated BALB.B and CXBE mice, 5 to 6 days after
transplantation of B6 T cells. Flow cytometric analysis of B6
BALB.B
TDL did not indicate expansion of any particular TCR Vß family,
whereas Vß10 and Vß14 families were significantly expanded in the
B6->CXBE TDL. However, PCR-based complementarity-determining region 3
size spectratyping revealed overlapping involvement of donor Vß1, 6,
8, 9, 10, and 14 families in both BALB.B and CXBE recipients and unique
utilization of the Vß4 family in BALB.B mice, suggesting oligoclonal
T cell responses to a limited number of miHA. In addition, the
injection of CD8+Vß14+ B6 T cells into
irradiated BALB.B and CXBE mice induced lethal GVHD, confirming the
involvement of miHA-specific T cells within an individual Vß family.
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