T-cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny.
To study the source of regenerated T cells after bone marrow transplantation (BMT), lethally irradiated thymectomized 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 V beta repertoire. Therefore, peripheral T-cell progenitors exist within V beta 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.
Mackall
C L
CL
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. 20892.
Granger
L
L
Sheard
M A
MA
Cepeda
R
R
Gress
R E
RE
D000818:Animals; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology; D018960:Hyaluronan Receptors; D017493:Leukocyte Common Antigens / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D012038:Regeneration; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*
D015704:CD4 Antigens; D018960:Hyaluronan Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing; D017493:Leukocyte Common Antigens