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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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Immunofluorescence profiles of bone marrow B cells and  thymocytes from PBS- and IFN-α2/α1–treated 129 Sv/Ev wild-type  (top) and IFN-α/β receptor−/− mice (bottom). Bone marrow cells were  stained with anti-μ and B220 antibodies, and thymocytes were stained  with anti-CD4 and anti-CD8. The percentages of cells within each quadrant are indicated.
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Figure 8: Immunofluorescence profiles of bone marrow B cells and thymocytes from PBS- and IFN-α2/α1–treated 129 Sv/Ev wild-type (top) and IFN-α/β receptor−/− mice (bottom). Bone marrow cells were stained with anti-μ and B220 antibodies, and thymocytes were stained with anti-CD4 and anti-CD8. The percentages of cells within each quadrant are indicated.

Mentions: To examine the possibility that these inhibitory effects on B and T lymphopoiesis could be attributable to nonspecific cytotoxicity of the recombinant IFN-α2/α1 preparation, we treated type I interferon receptor (IFN-α/ βR) knockout mice (129 Sv/Ev strain) with the recombinant IFN-α2/α1 protein under the same experimental conditions. When treated with IFN-α2/α1, the wild-type 129 mice had an even greater impairment in T and B cell development than did the BALB/c mice, thus suggesting strain differences in interferon sensitivity (Fig. 8). In contrast, T and B cell development was perfectly normal in mice lacking the IFN-α/β receptor after IFN-α2/α1 treatment (Fig. 8). This finding indicates that the inhibitory effect of IFN-α2/α1 on T and B cell development in wild-type mice is mediated via the IFN-α/β receptor.


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

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

Immunofluorescence profiles of bone marrow B cells and  thymocytes from PBS- and IFN-α2/α1–treated 129 Sv/Ev wild-type  (top) and IFN-α/β receptor−/− mice (bottom). Bone marrow cells were  stained with anti-μ and B220 antibodies, and thymocytes were stained  with anti-CD4 and anti-CD8. The percentages of cells within each quadrant are indicated.
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Related In: Results  -  Collection

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

Figure 8: Immunofluorescence profiles of bone marrow B cells and thymocytes from PBS- and IFN-α2/α1–treated 129 Sv/Ev wild-type (top) and IFN-α/β receptor−/− mice (bottom). Bone marrow cells were stained with anti-μ and B220 antibodies, and thymocytes were stained with anti-CD4 and anti-CD8. The percentages of cells within each quadrant are indicated.
Mentions: To examine the possibility that these inhibitory effects on B and T lymphopoiesis could be attributable to nonspecific cytotoxicity of the recombinant IFN-α2/α1 preparation, we treated type I interferon receptor (IFN-α/ βR) knockout mice (129 Sv/Ev strain) with the recombinant IFN-α2/α1 protein under the same experimental conditions. When treated with IFN-α2/α1, the wild-type 129 mice had an even greater impairment in T and B cell development than did the BALB/c mice, thus suggesting strain differences in interferon sensitivity (Fig. 8). In contrast, T and B cell development was perfectly normal in mice lacking the IFN-α/β receptor after IFN-α2/α1 treatment (Fig. 8). This finding indicates that the inhibitory effect of IFN-α2/α1 on T and B cell development in wild-type mice is mediated via the IFN-α/β receptor.

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