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Impairment of T and B cell development by treatment with a type I interferon.

Lin Q, Dong C, Cooper MD - J. Exp. Med. (1998)

Bottom Line: Correspondingly, IL-7-responsive cells in the bone marrow were virtually eliminated by the interferon treatment.Phenotypic analysis of the residual thymocytes indicated that the inhibitory effect was exerted during the pro-T cell stage in differentiation.The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

ABSTRACT
Type I interferons alpha and beta, naturally produced regulators of cell growth and differentiation, have been shown to inhibit IL-7-induced growth and survival of B cell precursors in vitro. After confirming an inhibitory effect on B lymphopoiesis in an ex vivo assay, we treated newborn mice with an active IFN-alpha2/alpha1 hybrid molecule to assess its potential for regulating B and T cell development in vivo. Bone marrow and splenic cellularity was greatly reduced in the IFN-alpha2/alpha1-treated mice, and B lineage cells were reduced by >80%. The bone marrow progenitor population of CD43+B220+HSA- cells was unaffected, but development of the CD19+ pro-B cells and their B lineage progeny was severely impaired. Correspondingly, IL-7-responsive cells in the bone marrow were virtually eliminated by the interferon treatment. Thymus cellularity was also reduced by >80% in the treated mice. Phenotypic analysis of the residual thymocytes indicated that the inhibitory effect was exerted during the pro-T cell stage in differentiation. In IFN-alpha/beta receptor-/- mice, T and B cell development were unaffected by the IFN-alpha2/alpha1 treatment. The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.

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In vitro analysis of B lymphopoiesis by fetal liver progenitor  cells in the presence or absence of IFN-α2/α1. IFN-α2/α1 (103 U/ml)  was added at the time of culture initiation and half of the medium was exchanged for fresh medium containing 103 U/ml IFN-α2/α1 every 7 d.  B220 and IgM expression was examined for the fetal liver cells derived  from day 15 embryos. The cells were cultured over a confluent layer of  IL-7–transfected T220 cells. Percentages of B220+ and IgM+ cells are indicated in the corresponding quadrants.
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Figure 1: In vitro analysis of B lymphopoiesis by fetal liver progenitor cells in the presence or absence of IFN-α2/α1. IFN-α2/α1 (103 U/ml) was added at the time of culture initiation and half of the medium was exchanged for fresh medium containing 103 U/ml IFN-α2/α1 every 7 d. B220 and IgM expression was examined for the fetal liver cells derived from day 15 embryos. The cells were cultured over a confluent layer of IL-7–transfected T220 cells. Percentages of B220+ and IgM+ cells are indicated in the corresponding quadrants.

Mentions: The effect of IFN-α/β treatment on B cell development was initially examined by incubating fetal liver–derived cells with IFN-α2/α1 (35). The activity of the human IFN-α2/α1 preparation was evaluated in a comparative analysis with mouse IFN-α/β to confirm similar inhibitory effects on IL-7–dependent cells and the absence of significant effect on other types of cytokine-dependent cells (reference 27 and data not shown). B lymphopoiesis by fetal liver progenitors was then monitored by the expression of B220 and IgM. At the time of culture initiation, 18% of the fetal liver cells were B220+ (Fig. 1). After 5 d of culture with the IL-7 fibroblast transfectants, nearly 90% of the cells in control cultures were B220+, whereas ∼50% of the IFN-α2/α1–treated cells were B220+. On days 10 and 15, 25% and 45% of the cells were IgM+B220+ B cells in the control cultures, respectively. By contrast, <10% of the IFN-α2/α1–treated cells were IgM+ by day 15. These results indicate that IFN-α2/α1 is an effective inhibitor of B lymphopoiesis ex vivo.


Impairment of T and B cell development by treatment with a type I interferon.

Lin Q, Dong C, Cooper MD - J. Exp. Med. (1998)

In vitro analysis of B lymphopoiesis by fetal liver progenitor  cells in the presence or absence of IFN-α2/α1. IFN-α2/α1 (103 U/ml)  was added at the time of culture initiation and half of the medium was exchanged for fresh medium containing 103 U/ml IFN-α2/α1 every 7 d.  B220 and IgM expression was examined for the fetal liver cells derived  from day 15 embryos. The cells were cultured over a confluent layer of  IL-7–transfected T220 cells. Percentages of B220+ and IgM+ cells are indicated in the corresponding quadrants.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199191&req=5

Figure 1: In vitro analysis of B lymphopoiesis by fetal liver progenitor cells in the presence or absence of IFN-α2/α1. IFN-α2/α1 (103 U/ml) was added at the time of culture initiation and half of the medium was exchanged for fresh medium containing 103 U/ml IFN-α2/α1 every 7 d. B220 and IgM expression was examined for the fetal liver cells derived from day 15 embryos. The cells were cultured over a confluent layer of IL-7–transfected T220 cells. Percentages of B220+ and IgM+ cells are indicated in the corresponding quadrants.
Mentions: The effect of IFN-α/β treatment on B cell development was initially examined by incubating fetal liver–derived cells with IFN-α2/α1 (35). The activity of the human IFN-α2/α1 preparation was evaluated in a comparative analysis with mouse IFN-α/β to confirm similar inhibitory effects on IL-7–dependent cells and the absence of significant effect on other types of cytokine-dependent cells (reference 27 and data not shown). B lymphopoiesis by fetal liver progenitors was then monitored by the expression of B220 and IgM. At the time of culture initiation, 18% of the fetal liver cells were B220+ (Fig. 1). After 5 d of culture with the IL-7 fibroblast transfectants, nearly 90% of the cells in control cultures were B220+, whereas ∼50% of the IFN-α2/α1–treated cells were B220+. On days 10 and 15, 25% and 45% of the cells were IgM+B220+ B cells in the control cultures, respectively. By contrast, <10% of the IFN-α2/α1–treated cells were IgM+ by day 15. These results indicate that IFN-α2/α1 is an effective inhibitor of B lymphopoiesis ex vivo.

Bottom Line: Correspondingly, IL-7-responsive cells in the bone marrow were virtually eliminated by the interferon treatment.Phenotypic analysis of the residual thymocytes indicated that the inhibitory effect was exerted during the pro-T cell stage in differentiation.The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

ABSTRACT
Type I interferons alpha and beta, naturally produced regulators of cell growth and differentiation, have been shown to inhibit IL-7-induced growth and survival of B cell precursors in vitro. After confirming an inhibitory effect on B lymphopoiesis in an ex vivo assay, we treated newborn mice with an active IFN-alpha2/alpha1 hybrid molecule to assess its potential for regulating B and T cell development in vivo. Bone marrow and splenic cellularity was greatly reduced in the IFN-alpha2/alpha1-treated mice, and B lineage cells were reduced by >80%. The bone marrow progenitor population of CD43+B220+HSA- cells was unaffected, but development of the CD19+ pro-B cells and their B lineage progeny was severely impaired. Correspondingly, IL-7-responsive cells in the bone marrow were virtually eliminated by the interferon treatment. Thymus cellularity was also reduced by >80% in the treated mice. Phenotypic analysis of the residual thymocytes indicated that the inhibitory effect was exerted during the pro-T cell stage in differentiation. In IFN-alpha/beta receptor-/- mice, T and B cell development were unaffected by the IFN-alpha2/alpha1 treatment. The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.

Show MeSH
Related in: MedlinePlus