T-Cell Regeneration After Bone Marrow Transplantation: Differential CD45 Isoform Expression on Thymic-Derived Versus Thymic-Independent Progeny

• Published in: Blood Vol. 82; no. 8; pp. 2585 - 2594
• Main Authors: Mackall, Crystal L., Granger, Lawrence, Sheard, Michael A., Cepeda, Rosemarie, Gress, Ronald E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.1993
• Subjects: Animals; Bone Marrow Transplantation; CD4 Antigens - analysis; Female; Hematopoietic Stem Cells - physiology; Hyaluronan Receptors; Leukocyte Common Antigens - analysis; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell, alpha-beta - analysis; Receptors, Lymphocyte Homing - analysis; Regeneration; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Thymus Gland - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.8.2585.2585

To study the source of regenerated T cells after bone marrow transplantation (BMT), lethally irradiated thymec-tomized and thymus-bearing C57BL/6 (Thy 1.2+) mice were injected with syngeneic T-cell depleted bone marrow (TCD BM) cells and graded numbers of congenic B6/Thy 1.1 + lymph node (LN) cells. LN cell expansion was the predominant source for T-cell regeneration in thymectomized hosts but was minimal in thymus-bearing hosts. Analysis of T-cell receptor (TCR) expression on LN progeny showed a diverse Vβ repertoire. Therefore, peripheral T-cell progenitors exist within Vβ families, but expansion of these progenitors after BMT is downregulated in the presence of a functional thymus. CD4+ cells derived from BM versus LN in thymus-bearing hosts displayed differential CD44 and CD45 isoform expression. BM-derived cells were primarily CD45RB+CD44lo and LN derived cells were nearly exclusively CD45RB-CD44hi. In thymectomized hosts, BM, host, and LN CD4+ progeny were CD45RB-CD44hi. We conclude that T-cell regeneration via peripheral T-cell progenitors predominates in hosts lacking thymic function and gives rise to T cells that display a “memory” phenotype. In contrast, the ability to generate sizable populations of “naive” type T cells after BMT appears limited to the prethymic progenitor pool and could serve as a marker for thymic regenerative capacity. This is a US government work. There are no restrictions on its use.