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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1122-1126
IMMUNOBIOLOGY
Peripheral blood stem cell allograft rejection mediated by
CD4+ T lymphocytes recognizing a single mismatch at
HLA-DP 1*0901
Katharina Fleischhauer,
Elisabetta Zino,
Benedetta Mazzi,
Elisabetta Sironi,
Paolo Servida,
Elisabetta Zappone,
Elena Benazzi, and
Claudio Bordignon
From the HLA Tissue Typing Laboratory and the BMT-Unit,
Istituto Scientifico H.S. Raffaele; and the San Raffaele Telethon
Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
Little is known about the molecular characteristics of alloantigens
recognized by alloreactive T cells mediating hematologic stem cell
graft rejection. In particular, it has never been shown that such
alloantigens can be encoded by HLA-DP alleles. Indeed, matching for
HLA-DP antigens is generally not considered to be of functional
importance for the outcome of allogeneic bone marrow or peripheral
blood stem cell transplantation. In this study, a case of peripheral
blood stem cell allograft rejection was investigated in which the
patient and donor differed for a single mismatch at HLA-DP in the
rejection direction. Patient-derived T lymphocytes circulating at the
time of rejection showed direct ex vivo cytotoxic activity against
donor-derived B-lymphoblastoid cells as well as other
HLA-DP1*0901-expressing targets. The presence of
HLA-DP1*0901-specific effectors in vivo was further confirmed by in
vitro stimulation experiments. CD4+ T-cell lines and clones
with specific cytotoxic activity against HLA-DP1*0901-expressing
targets including donor B-lymphoblastoid cells were generated both by
nonspecific and by donor-specific in vitro stimulation. Taken together,
these data demonstrate that HLA-DP can be the target antigen of
cytotoxic CD4+ T lymphocytes involved in peripheral blood
stem cell allograft rejection.
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