Specificity of T cells invading the skin during acute graft-vs.-host disease after semiallogeneic bone marrow transplantation.

Gaschet, Joëlle; Mahé, Brice; Milpied, Noël; Devilder, Marie‐Claire; Dréno, Brigitte; Bignon, J.; Davodeau, François; Hallet, Marie‐Martine; Bonneville, Marc; Vié, Henri

doi:10.1172/jci116160

Cited by 29 publications

(21 citation statements)

References 33 publications

(11 reference statements)

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“…1), these results strongly suggested that each set of clones belonging to the same TCRBV family derived in fact from a single or a few T cell clones. These findings are also in agreement with our previous reports showing that T cells infiltrating the skin at the onset of GVHD were oligoclonal, and for a majority of them, host specific (11,12). Consequently, one clone representative of each subset was kept for further characterization.…”

Section: Origin and Specificity Of Clones Derived From Bil T Lymphocysupporting

confidence: 93%

“…We have recently documented the presence of HLA-DP-specific T cells in the skin lesions of patients who developed GVHD after semiallogeneic BMT (11,12). In these previous examples, other HLA class I and class II incompatibilities were present in addition to the HLA-DP mismatch.…”

Section: Discussionmentioning

confidence: 99%

“…Because the viral TK is able to phosphorylate the nucleoside analogue ganciclovir, resulting in the production of metabolites toxic for mammalian cells, its transfer into T cells renders them sensitive to ganciclovir and allows their destruction through ganciclovir treatment (28). In line with these concerns, how can we take advantage of these two apparently paradoxical observations: HLA-DP incompatibility does not significantly influence the risk of acute GVHD (9, 10), yet HLA-DP specific T cells can be isolated from skin biopsies at the onset of GVHD each time an HLA-DP mismatch is present (11,12, and this report). If an HLA-DP mismatch is able to induce an allogeneic response in vivo it should be able to trigger both a GVH and a GVL effect (as long as the leukemic cells express the HLA-DP antigens, of course).…”

Section: Discussionmentioning

confidence: 99%

“…These conditions, where 100% of T cells are stimulated, were chosen to avoid in vitro antigenic selection. This allows the best representation of T cells, which grew under rIL-2 alone during the initial culture period, i.e., the in vivo activated T cells infiltrating the biopsy (11,12), since this procedure was shown to preserve the initial diversity of the amplified population (13). Before specificity assays, clones were cultured in IL-2 alone without stimulation for at least 3 wk.…”

Section: Obtaining Skin Infiltrating T Cells and Clonesmentioning

confidence: 99%

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Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Gaschet¹,

Lim²,

Liem³

et al. 1996

J. Clin. Invest.

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Analysis of a large number of unrelated bone marrow transplantations (BMT) has shown that HLA-DP incompatibility did not detectably influence the risk for acute graft-versushost disease (aGVHD). Accordingly, it was proposed that HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B, or -DR. We have previously shown that HLA-DP (as well as HLA-A, -B, -DQ, or -DR)-specific T cells could be isolated from skin biopsies of patients who developed an aGVHD after semiallogeneic BMT. Nevertheless, whether a single HLA-DP mismatched allele could induce a detectable allo-specific reaction in vivo after BMT remained to be established. To directly address this issue we studied one patient who presented aGVHD after receiving purified CD34 ϩ bone marrow (BM) cells from an unrelated donor with a single HLA-DP mismatch in the GVHD direction. To characterize the immunological events associated with GVHD, we analyzed the peripheral T cell repertoire, the T cell receptor V ␤ diversity, and the specificity of T cells invading a skin biopsy at the onset of GVHD. Our results demonstrated that a large fraction of skin-infiltrating lymphocytes, which expressed diverse T cell receptors, were reactive against this single HLA-DPB1*0501 mismatch and consequently that a single HLA-DP mismatch between BM donor and recipient can activate a strong T cell response in vivo. ( J. Clin. Invest. 1996. 98:100-107.)

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Section: Origin and Specificity Of Clones Derived From Bil T Lymphocysupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Obtaining Skin Infiltrating T Cells and Clonesmentioning

confidence: 99%

See 2 more Smart Citations

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Gaschet¹,

Lim²,

Liem³

et al. 1996

J. Clin. Invest.

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“…Indeed, we have demonstrated the presence of HLA-DP-specific T cells in the skin of patients who developed GVHD after semi-allogeneic BMT, each time an HLA-DP mismatch was present. [6][7][8] However, only once did we have the opportunity to analyze a graft setting where HLA-DP was the only documented mismatch in the GVHD direction. In that case, we could demonstrate that a large fraction of skin-infiltrating T lymphocytes expressing diverse T cell receptors were reactive against HLA-DPB1*0501, the only mismatch of the graft.…”

mentioning

confidence: 99%

Acute graft-versus-host disease after bone marrow transplantation with a single HLA-DPB1*1001 mismatch: involvement of different TCRBV subsets

Gaschet

Gallot

Ibisch

et al. 1998

Bone Marrow Transplant

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Summary:HLA-DP incompatibility is not considered as an exclusion criterion for bone marrow donors, because such incompatibility was not shown to affect significantly the risk for acute graft-versus-host disease (GVHD). In line with this clinical observation, it was proposed that in the context of bone marrow transplantation, HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B or -DR. In contrast to the above conclusion, we recently demonstrated the presence of HLA-DPB1*0501 specific T cell clones in a skin biopsy of a patient who developed aGVHD after receiving a bone marrow transplant (BMT) in which the only mismatched allele in the GVHD direction was HLA-DPB1*0501. At that time, this case was unique and occurred in a relatively uncommon graft setting where the patient received purified CD34 + BM cells from an unrelated donor. In the present study, we analyzed the immunological events associated with an aGVHD which occurred in the context of a 'regular' allogeneic BMT involving a single HLA-DPB1*1001 mismatch between donor and recipient in the GVHD direction. To this end, we analyzed several amplified T cell subsets present within a T cell line derived from a skin biopsy performed at the onset of GVHD. Our results demonstrated that T cell populations belonging to the TCRBV2, TCRB6.7, TCRBV14 and TCRBV17 subsets were specific for the HLA-DPB1*1001 mismatched allele. These data strengthen and generalize our first conclusion that a single HLA-DP mismatch between donor and recipient can activate a strong T cell response in vivo and consequently challenge the notion that HLA-DP incompatibility should not be taken into account in the choice of BM donors. Moreover, they also underline the idea that HLA-DP antigens may represent an interesting immune target for future therapeutic approaches. Keywords: transplantation; HLA-DP; GVH Allogeneic bone marrow transplantation (BMT) can be successfully used to treat patients with several hematologic malignancies or severe aplastic anaemia. The major complication of this procedure is graft-versus-host disease (GVHD) with a risk of 20-50% when donor and recipient are HLA-identical siblings. 1 When no HLA-identical sibling is available (which is the case for more than 60% of patients), matched or partially mismatched unrelated donors represent an alternative source of bone marrow. 2,3 Unfortunately, the rate of GVHD and rejection appears to increase with the extent of HLA mismatch. With respect to HLA disparities, the increased risk of aGVHD associated with HLA-A, -B, -DR mismatches between donor and recipient is well established. 2 In contrast, concerning HLA-DP incompatibility, conclusions drawn from clinical statistics or biological data are apparently conflicting: although severe GVHD following HLA-DP incompatible, but otherwise HLA-identical, BMT has been reported by several groups, recent analysis of a large series of patients did not confirm that HLA-DP antigens played a significant role in the incidence of severe acute GVHD (see Re...

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Cutaneous Graft-versus-Host Disease

Aractingi

Chosidow²

1998

Arch Dermatol

184

177

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Specificity of T cells invading the skin during acute graft-vs.-host disease after semiallogeneic bone marrow transplantation.

Cited by 29 publications

References 33 publications

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Acute graft-versus-host disease after bone marrow transplantation with a single HLA-DPB1*1001 mismatch: involvement of different TCRBV subsets

Cutaneous Graft-versus-Host Disease

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