Peripheral blood stem cell allograft rejection mediated by CD4(+) T lymphocytes recognizing a single mismatch at HLA-DP beta 1*0901.

Abstract:

: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 beta 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-DP beta 1*0901--expressing targets. The presence of HLA-DP beta 1*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-DP beta 1*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. (Blood. 2001;98:1122-1126)

journal_name

Blood

journal_title

Blood

authors

Fleischhauer K,Zino E,Mazzi B,Sironi E,Servida P,Zappone E,Benazzi E,Bordignon C

doi

10.1182/blood.v98.4.1122

subject

Has Abstract

pub_date

2001-08-15 00:00:00

pages

1122-6

issue

4

eissn

0006-4971

issn

1528-0020

journal_volume

98

pub_type

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