scholarly journals Of Mice, Not Men: No Evidence for Graft-versus-Host Disease in Humans Receiving T-Cell Receptor–Transduced Autologous T Cells

2010 ◽  
Vol 18 (10) ◽  
pp. 1744-1745 ◽  
Author(s):  
Steven A Rosenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host

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

T cell receptor excision circle levels in CD94-expressing CD8 T Cells during graft-versus-host disease

2008 ◽  
Vol 49 (7) ◽  
pp. 1306-1310 ◽  
Author(s):  
Junichi Sugita ◽  
Noriaki Iwao ◽  
Junji Tanaka ◽  
Naoko Kato ◽  
Souichi Shiratori ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
Host Disease ◽  
Graft Versus Host

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(GVHD) skin lesions show a bias in the usage of TCR V beta families, whereas examination of peripheral blood (PB) withdrawn at the same time did not reveal a similar phenomenon.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.

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

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.

PD-L1 and PD-L2 Protect The Heart In a T-Cell Receptor Transgenic Model Of Graft-Versus Host Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4479-4479
Author(s):  
Kathryn W Juchem ◽  
Britt Anderson ◽  
Cuiling Zhang ◽  
Arlene Sharpe ◽  
Jennifer McNiff ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Weight Loss ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Graft Versus Host Disease ◽  
Cell Receptor ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Donor Bone Marrow

Graft-versus-host disease (GVHD) is a complication of allogeneic stem cell transplantation (alloSCT). In murine models of alloSCT, naive T cells (TN) cause GVHD while effector memory T cells (TEM) do not. To determine why TEM fail to cause GVHD, we generated a novel T-cell receptor transgenic GVHD model. In this model CD4+ TS1 T cells, which recognize an epitope of influenza hemagglutinin (HA), are transferred, along with syngeneic bone marrow, into irradiated transgenic recipients that express HA in all tissues (HA104 Tg mice). We found that TS1 TN induced early and prolonged weight loss and caused GVHD-like pathology in the skin, liver and colon. In contrast, TS1 TEM induced mild, transient weight loss and minimal pathology, demonstrating that TEM have repertoire-independent characteristics that limit their ability to induce GVHD. Post transplant analysis revealed that TS1 TEM progeny, relative to TS1 TN progeny, produced less IFN-γ, proliferated and accumulated less in the colon, and expressed higher levels of the inhibitory molecule PD-1. To investigate whether PD-1 was responsible for limiting pathogenesis by TEM, we used hosts and donor bone marrow lacking both PD-L1 and PD-L2. The absence of PD-L1/2 did not enable TS1 TEM to cause early weight loss. However, between 35 and 60 days post transplant, TS1 TEM recipients lacking PD-L1/2 rapidly began losing weight and approximately 50% died. Weight loss in TEM recipients was dependent upon lack of PD-L1/2 expression on both donor bone marrow and host cells, including radioresistant stromal cells, suggesting a possible role for PD-L1/2 expressed in tissues. Indeed, global absence of PD-L1 alone, which (in contrast to PD-L2) is expressed on parenchymal tissues, also resulted in late weight loss in recipients given TEM. To determine the reason for late weight loss, we surveyed tissue histopathology. Surprisingly, in the absence of PD-L1/2, TEM recipients did not develop exacerbated colon pathology but instead developed mononuclear infiltrates and mycocyte necrosis in the heart, accompanied by heart block and decreased cardiac output. Interestingly, heart disease was also seen in PD-L1/2 deficient TN recipients that survived to later time points, indicating that the protective role of PD-L1/2 applied more generally to GVHD induced by CD4 T cells. Strikingly, the extensive infiltrates in affected hearts were mostly comprised of non-TS1 T cells, including both CD4 and CD8 cells. These cells are likely host-derived, as severe cardiac infiltrates were seen when Rag-deficient donor BM was used to reconstitute host hematopoiesis. We therefore hypothesize that in GVHD PD-L1/2 normally prevent “allogeneic” T cell mediated damage but also protect from subsequent syngeneic T cell-mediated pathogenesis that could contribute to prolonged disease. This effect is tissue specific and could in part be due to parenchymal expression of PD-L1 in certain organs. It is possible that such mechanisms could explain more chronic phases of GVHD, which differs from acute GVHD. Ongoing depletion experiments will determine the relative contributions of donor TS1 T cells, donor bone marrow derived T cells and host T cells. Disclosures: No relevant conflicts of interest to declare.

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