Preemptive administration of human αβ T cell receptor-targeting monoclonal antibody GZ-αβTCR potently abrogates aggressive graft-versus-host disease in vivo

2015 ◽  
Vol 94 (11) ◽  
pp. 1907-1919 ◽  
Author(s):  
Gregor Blank ◽  
Christian Welker ◽  
Bence Sipos ◽  
Katja Sonntag ◽  
Friederike Müller ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Receptor Targeting ◽  
Host Disease ◽  
Graft Versus Host

Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor

1991 ◽  
Vol 34 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Dietrich W. Beelen ◽  
Hans Grosse-Wilde ◽  
Ursula Ryschka ◽  
Klaus Quabeck ◽  
Herbert G. Sayer ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Initial Treatment ◽  
Cell Receptor ◽  
Murine Monoclonal Antibody ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Treatment of Acute Graft-Versus-Host Disease After HLA-Partially Matched Marrow Transplantation with a Monoclonal Antibody (BMA031) Against the T Cell Receptor

1988 ◽  
Vol 11 (1) ◽  
pp. 56-58 ◽  
Author(s):  
D.W. Beelen ◽  
U. Graeven ◽  
G. Schulz ◽  
H. Grosse-Wilde ◽  
I. Doxiadis ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals Molecular analysis of T-cell receptor repertoire in bone marrow transplant recipients: evidence for oligoclonal T-cell expansion in graft-versus-host disease lesions

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 3032-3044 ◽  
Author(s):  
X Liu ◽  
V Chesnokova ◽  
SJ Forman ◽  
DJ Diamond
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Supporting Evidence ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Beta 2

We have analyzed the T-cell receptor (TCR) V beta repertoire using polymerase chain reaction (PCR) in a cohort of eight patients receiving allogeneic bone marrow transplantation (BMT) from related and unrelated donors at the City of Hope. Results of PCR studies from graft-versus- host disease (GVHD) skin lesions show a bias in the usage of TCR V beta families, whereas examination of peripheral blood (PB) withdrawn at the same time did not reveal a similar phenomenon. In one such family, TCR V beta 2 is predominantly expressed in 7 of 7 biopsy specimens examined. V beta 2 TCR expression from these patients was analyzed more extensively using a combination of individual TCR gene cloning, followed by sequence analysis. We found evidence of oligoclonal expansion of single V beta 2-bearing TCRs in GVHD lesions, and in the PB of some patients after diagnosis of GVHD. In contrast, GVHD-negative biopsy samples showed no evidence for clonotypic TCR amplification. Sequence-specific TCR CDR3 region probes were derived from analysis of the predominant expressed TCR in GVHD lesions, and used to probe Southern blots of amplified V beta 2 TCR mRNA from PB and tissue from BMT recipients and their respective donors. In most cases the probes are highly specific in detecting TCR expression from GVHD lesions alone, although in several instances expression could be detected in PB after GVHD diagnosis. These data provide supporting evidence for the hypothesis that acute GVHD is associated with expansion of T-cell clones expressing antigen-specific TCRs that may contribute to the disease pathology.

THE FATE OF DONOR T-CELL RECEPTOR TRANSGENIC T CELLS WITH KNOWN HOST ANTIGEN SPECIFICITY IN A GRAFT-VERSUS-HOST DISEASE MODEL1

1999 ◽  
Vol 68 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Bimalangshu Dey ◽  
Yong-Guang Yang ◽  
Frederic Preffer ◽  
Akira Shimizu ◽  
Kirsten Swenson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Host Disease ◽  
Graft Versus Host

SELECTIVE T-CELL-RECEPTOR GENE USAGE IN ALLORECOGNITION AND GRAFT-VERSUS-HOST DISEASE

1993 ◽  
Vol 55 (5) ◽  
pp. 1167-1175 ◽  
Author(s):  
KATSUO YAMANAKA ◽  
WILLIAM W. KWOK ◽  
ERIC M. MICKELSON ◽  
SUSAN MASEWICZ ◽  
FRANK SMITH ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gene Usage ◽  
T Cell Receptor Gene ◽  
Cell Receptor Gene

Restricted use of T-cell receptor V beta genes in posttransfusion graft- versus-host disease

Transfusion ◽  
1997 ◽  
Vol 37 (11-12) ◽  
pp. 1184-1191 ◽  
Author(s):  
L Wang ◽  
K Tadokoro ◽  
K Tokunaga ◽  
S Uchida ◽  
S Moriyama ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Restricted Use

scholarly journals HLA-target antigens and T-cell receptor diversity of activated T cells invading the skin during acute graft-versus-host disease

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
J Gaschet ◽  
MA Trevino ◽  
M Cherel ◽  
R Vivien ◽  
A Garcia-Sahuquillo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Allogeneic Bone ◽  
T Cell Clones ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Clones

To study the repertoire and specificity of T lymphocytes infiltrating skin lesions during graft-versus-host disease (GVHD), we performed an exhaustive molecular and functional analysis of 146 T-cell clones derived from the skin of three patients undergoing an acute GVHD after allogeneic bone marrow transplantation (BMT) from HLA-mismatched related donors. Analysis of T-cell receptor (TCR) rearrangement and TCR chain junctional sequences demonstrated the presence of 11 distinct clones among the 64 derived from patient UPN1, six among the 58 derived from patient UPN2, and seven among the 24 derived from patient UPN3. Three of the 11 T-cell clones from patient UPN1, and all clones from patients UPN2 and UPN3 reacted with mismatched HLA alleles between the bone-marrow donor and recipient. Moreover, both HLA class I (HLA-A2 and -B27) and class II (HLA DP101, DP401, DP1301, DQ8, and DR402) molecules were recognized during this early antihost response. Finally, both TCR alpha and beta chains turned out to be extremely diverse, even within populations of clones derived from the same patient and directed against the same HLA allele. Taken together, these results indicate that any HLA mismatch is potentially targeted during early GVHD, and that the T-cell response at the onset of GVHD is both oligoclonal and highly diversified.

Anti-idiotypic antibody to T-cell receptor in multiply transfused patients may play a role in resistance to graft-versus-host disease

Transfusion ◽  
2003 ◽  
Vol 32 (8) ◽  
pp. 719-728 ◽  
Author(s):  
M. NISHIMURA ◽  
K. SAKAI ◽  
T. AKAZA ◽  
Y. MITOMI ◽  
M. NIEDA ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Idiotypic Antibody

scholarly journals Treatment of donor mice with an alpha beta T-cell receptor monoclonal antibody induces prolonged T-cell nonresponsiveness and effectively prevents lethal graft-versus-host disease in murine recipients of major histocompatibility complex (MHC)-matched and MHC-mismatched donor marrow grafts

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5355-5369 ◽  
Author(s):  
WR Drobyski ◽  
D Majewski
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antibody Treatment ◽  
Graft Versus Host ◽  
Histocompatibility Complex ◽  
T Cell Reconstitution

The purpose of this study was to determine whether the administration of high doses of an anti-T-cell receptor (TCR) monoclonal antibody (H57– 597) to donor animals could induce a state of T-cell nonresponsiveness and prevent the development of graft-versus-host disease (GVHD) in murine recipients of major histocompatibility complex (MHC)-matched (B10.BR[H-2k] --> AKR/J[H-2k]) and mismatched (B10.BR[H-2k] --> DBA/2[H- 2d]) marrow grafts. Transplantation of H57–597-treated B10.BR T cells into irradiated AKR or DBA mice resulted in protection from GVHD, which was otherwise lethal in transplanted recipients receiving untreated T cells. The administration of H57–597-treated T cells did not compromise alloengraftment in either strain combination and was found to accelerate donor T-cell reconstitution in recipients of MHC-matched marrow grafts. Optimal protection for GVHD was dependent on the duration of antibody exposure in donor mice. T cells from donor exposed to antibody for only 1 day caused lethal GVHD, whereas exposure for at least 4 days was necessary to abrogate graft-versus-host reactivity. The ability of antibody treatment to protect against the development of GVHD could not be ascribed to the antibody-induced production of Th2 cytokines, the induction of a T- or non-T-suppressor cell population, or the preferential depletion of CD4+ T cells by H57–597. Donor T cells exposed to H57–597 antibody were detectable in recipients for up to 5 weeks after transplantation, indicating that these cells were not eliminated in the host immediately after bone marrow transplantation and contributed to enhanced donor T-cell reconstitution. Moreover, in B10.BR --> DBA chimeras that did not have any clinical evidence of GVHD, potentially MIs-reactive donor-derived Vbeta6+ T cells were present in the spleens of recipients at comparable numbers to normal mice but appeared functionally nonresponsive in vivo. These data strongly suggested that protection from GVHD was due to the fact that antibody treatment resulted in a state of prolonged T-cell anergy that persisted despite the presence of potential costimulatory signals in the recipient. This observation is of potential clinical significance in that it shows that the prevention of GVHD can be accomplished without posttransplantation immunosuppression or the need for in vitro or in vivo T-cell depletion.

scholarly journals Oligoclonal expansion of T cell receptor V beta 2 and 3 cells in the livers of mice with graft-versus-host disease

Hepatology ◽  
2002 ◽  
Vol 35 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Weiran Chen ◽  
Charles D. Howell
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Beta 2 ◽  
Oligoclonal Expansion
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