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Thymic and extrathymic differentiation and expansion of T lymphocytes following bone marrow transplantation in irradiated recipients.
Exp Hematol. 1997 Aug; 25(9):992-1004.EH

Abstract

Thymic function is severely impaired in most marrow transplant recipients. To evaluate the impact of thymic hypoplasia on T cell reconstitution following marrow transplantation, we compared the phenotype and function of T lymphocytes in thymectomized recipients with those of euthymic hosts. Irradiated C57BL/6 mice (Thy1.2+, Ly5.1+) received 10(7) T cell-depleted B6.Ly5.2 bone marrow cells (Thy1.2+, Ly5.2+), with or without 3 x 10(5) B6.PL lymph node cells (Thy1.1+, Ly5.1+) as a source of T lymphocytes. Multiparameter flow cytometry analysis showed that in euthymic mice (group 1), T cell reconstitution was carried out by donor hematopoietic stem cells that differentiated in the host's thymus, whereas the production of chimeric T cells in athymic recipients depended on the presence or absence of T cells in the graft. When T lymphocytes were present in the graft (group 2), their progeny constituted the vast majority of splenic T cells on day 100 posttransplant. When the graft did not contain T lymphocytes (group 3), T cell reconstitution resulted from extrathymic maturation of donor hematopoietic progenitors; T cells differentiating along this pathway expressed lower levels of T cell receptor and a large proportion of the CD8+ subset expressed CD8alpha alpha homodimers. The T cell receptor Vbeta profile of all chimeras was similar to that of normal C57BL/6 mice. Compared with T cells found in euthymic recipients, those in mice from groups 2 and 3 were less abundant (particularly with respect to the CD4+ subset), displayed the CD44/CD45 phenotype of activated memory cells, and expressed high levels of IL-2 receptor beta chain. These results show that both the presence or absence of the thymus and the composition of the grafted inoculum determine the source and extent of posttransplant T cell reconstitution. Because they determine the nature of the differentiation pathway taken during T cell development in the host, these two factors can exert a critical influence on the appearance of graft vs. host disease and the level of host immunocompetence.

Authors+Show Affiliations

Department of Medicine, University of Montreal, and Research Center, Maisonneuve-Rosemont Hospital, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9257813

Citation

Dulude, G, et al. "Thymic and Extrathymic Differentiation and Expansion of T Lymphocytes Following Bone Marrow Transplantation in Irradiated Recipients." Experimental Hematology, vol. 25, no. 9, 1997, pp. 992-1004.
Dulude G, Brochu S, Fontaine P, et al. Thymic and extrathymic differentiation and expansion of T lymphocytes following bone marrow transplantation in irradiated recipients. Exp Hematol. 1997;25(9):992-1004.
Dulude, G., Brochu, S., Fontaine, P., Baron, C., Gyger, M., Roy, D. C., & Perreault, C. (1997). Thymic and extrathymic differentiation and expansion of T lymphocytes following bone marrow transplantation in irradiated recipients. Experimental Hematology, 25(9), 992-1004.
Dulude G, et al. Thymic and Extrathymic Differentiation and Expansion of T Lymphocytes Following Bone Marrow Transplantation in Irradiated Recipients. Exp Hematol. 1997;25(9):992-1004. PubMed PMID: 9257813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thymic and extrathymic differentiation and expansion of T lymphocytes following bone marrow transplantation in irradiated recipients. AU - Dulude,G, AU - Brochu,S, AU - Fontaine,P, AU - Baron,C, AU - Gyger,M, AU - Roy,D C, AU - Perreault,C, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 992 EP - 1004 JF - Experimental hematology JO - Exp Hematol VL - 25 IS - 9 N2 - Thymic function is severely impaired in most marrow transplant recipients. To evaluate the impact of thymic hypoplasia on T cell reconstitution following marrow transplantation, we compared the phenotype and function of T lymphocytes in thymectomized recipients with those of euthymic hosts. Irradiated C57BL/6 mice (Thy1.2+, Ly5.1+) received 10(7) T cell-depleted B6.Ly5.2 bone marrow cells (Thy1.2+, Ly5.2+), with or without 3 x 10(5) B6.PL lymph node cells (Thy1.1+, Ly5.1+) as a source of T lymphocytes. Multiparameter flow cytometry analysis showed that in euthymic mice (group 1), T cell reconstitution was carried out by donor hematopoietic stem cells that differentiated in the host's thymus, whereas the production of chimeric T cells in athymic recipients depended on the presence or absence of T cells in the graft. When T lymphocytes were present in the graft (group 2), their progeny constituted the vast majority of splenic T cells on day 100 posttransplant. When the graft did not contain T lymphocytes (group 3), T cell reconstitution resulted from extrathymic maturation of donor hematopoietic progenitors; T cells differentiating along this pathway expressed lower levels of T cell receptor and a large proportion of the CD8+ subset expressed CD8alpha alpha homodimers. The T cell receptor Vbeta profile of all chimeras was similar to that of normal C57BL/6 mice. Compared with T cells found in euthymic recipients, those in mice from groups 2 and 3 were less abundant (particularly with respect to the CD4+ subset), displayed the CD44/CD45 phenotype of activated memory cells, and expressed high levels of IL-2 receptor beta chain. These results show that both the presence or absence of the thymus and the composition of the grafted inoculum determine the source and extent of posttransplant T cell reconstitution. Because they determine the nature of the differentiation pathway taken during T cell development in the host, these two factors can exert a critical influence on the appearance of graft vs. host disease and the level of host immunocompetence. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/9257813/Thymic_and_extrathymic_differentiation_and_expansion_of_T_lymphocytes_following_bone_marrow_transplantation_in_irradiated_recipients_ DB - PRIME DP - Unbound Medicine ER -