Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation.

Abstract

We found that c-kit-positive, lineage marker-negative, Thy-1lo cells are present in both bone marrow and thymus ("BM c-kit" and "thymus c-kit" cells). Although the two cell types are phenotypically similar, only BM c-kit cells showed the potential to form colonies in vitro as well as in vivo. However, both of them revealed extensive growth and differentiation potential to T cells after direct transfer into an irradiated adult thymus, or a deoxyguanosine-treated fetal thymus. Time course analysis showed that thymus c-kit cells differentiated into CD4CD8 double-positive cells approximately 4 d earlier than BM c-kit cells did. In addition, anti-c-kit antibody blocked T cell generation of BM c-kit cells but not of thymus c-kit cells. Intravenous injection of thymus c-kit resulted in the generation of not only T cells, but B as well as NK1.1+ cells. These data provide evidence that thymus c-kit cells represent common lymphoid progenitors with the differentiation potential to T, B, and possibly NK cells. The c-kit-mediated signaling appears to be essential in the transition from BM c-kit to thymus c-kit cells.

CD56+ CD7+ Stem Cell Leukemia/Lymphoma with D2-J.DELTA.1 Rearrangement.

“…In the current study, patients' blasts apparently correspond to prothymocyte stage I (pro-T I) in T-cell development proposed by Haynes et al (35). The Pro-T population probably includes a small fraction of CLPs (41,42). All patients' blasts had incomplete D52J81rearrangementat least on one allele even in the absence of CyCD3e(2/2).…”

Extensive proliferation of T cell lineage‐restricted progenitors in the thymus: an essential process for clonal expression of diverse T cell receptor β chains

“…Since early thymic progenitors express c-kit and IL-7R [28,29], the ligands for these receptors have been predicted to be involved in the expansion of progenitors at early stages. In fact, the requirement of stem cell factor and IL-7 as well as the synergistic effect of these two factors on progenitor expansion, was demonstrated [10,11,30].…”

Expression and regulation of c-kit receptor and response to stem cell factor in childhood malignant T-lymphoblastic cells

“…14 In combination with IL-7, SCF was found to be a potent stimulus at early stages of T and B lymphoid development. 7,[15][16][17][18][19][20][21][22] In mice, T cell proliferation occurred in a population of IL2R + /CD4 − /CD8 − /CD3 − thymocytes by the combination of IL-7 and SCF. 20 A high level of c-kit expression defines pro-T cells which have not yet rearranged their TCR genes.…”

“…In the same study, anti-c-kit antibody blocked T cell generation of c-kit + bone marrow cells, but not of c-kit + thymus cells. 22 The growth conditions of T cell lymphoma or leukemia and their dependence on growth factors are of interest, because cytokines are being added to chemotherapy protocols for treatment of patients with these conditions. The cytokine SCF was tested in phase I clinical trials as an adjunct in the therapy of malignant disease.…”