Abstract
Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 107 spleen cells plus 3 x 107 bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,D(d); Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of Vβ11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of Vβ11+ T cells terminated by 180 days after tolerance induction. Vβ11+ T cells which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with Vβ11-specific mAb. Furthermore, the CTL activity against class I (D(d)) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (D(d)) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.
| Original language | English |
|---|---|
| Pages (from-to) | 4026-4036 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 145 |
| Issue number | 12 |
| Publication status | Published - Dec 1 1990 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
Cite this
Evidence for involvement of clonal anergy in MHC class I and class II disparate skin allograft tolerance after the termination of intrathymic clonal deletion. / Tomita, Y.; Nishimura, Y.; Harada, N.; Eto, M.; Ayukawa, K.; Yoshikai, Y.; Nomoto, K.
In: Journal of Immunology, Vol. 145, No. 12, 01.12.1990, p. 4026-4036.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence for involvement of clonal anergy in MHC class I and class II disparate skin allograft tolerance after the termination of intrathymic clonal deletion
AU - Tomita, Y.
AU - Nishimura, Y.
AU - Harada, N.
AU - Eto, M.
AU - Ayukawa, K.
AU - Yoshikai, Y.
AU - Nomoto, K.
PY - 1990/12/1
Y1 - 1990/12/1
N2 - Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 107 spleen cells plus 3 x 107 bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,D(d); Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of Vβ11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of Vβ11+ T cells terminated by 180 days after tolerance induction. Vβ11+ T cells which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with Vβ11-specific mAb. Furthermore, the CTL activity against class I (D(d)) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (D(d)) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.
AB - Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 107 spleen cells plus 3 x 107 bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,D(d); Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of Vβ11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of Vβ11+ T cells terminated by 180 days after tolerance induction. Vβ11+ T cells which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with Vβ11-specific mAb. Furthermore, the CTL activity against class I (D(d)) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (D(d)) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.
UR - http://www.scopus.com/inward/record.url?scp=0025610843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025610843&partnerID=8YFLogxK
M3 - Article
C2 - 2147933
AN - SCOPUS:0025610843
VL - 145
SP - 4026
EP - 4036
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -