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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 profile analysis of B lineage cells in the  bone marrow and spleen of PBS- and IFN-α2/α1–treated mice. Cells  were stained with FITC-conjugated anti-μ and Cy-chrome–labeled anti-B220 and the immunocytometric analysis was limited to cells with the  forward and side light scattering characteristics of lymphocytes. Percentages of IgM−B220+ and IgM+B220+ cells in the boxed areas are indicated.
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Figure 3: Immunofluorescence profile analysis of B lineage cells in the bone marrow and spleen of PBS- and IFN-α2/α1–treated mice. Cells were stained with FITC-conjugated anti-μ and Cy-chrome–labeled anti-B220 and the immunocytometric analysis was limited to cells with the forward and side light scattering characteristics of lymphocytes. Percentages of IgM−B220+ and IgM+B220+ cells in the boxed areas are indicated.

Mentions: An ∼50% decrease in the percentage of B220+IgM+ B cells was observed for the bone marrow and splenic lymphocyte populations in the IFN-α2/α1–treated neonates (Fig. 3). Reductions in the absolute number of B cells were estimated to be 89 and 84% in the bone marrow and spleen, respectively. Although the percentage of residual B220+IgM− B lineage cells was only modestly decreased in the bone marrow of IFN-α2/α1–treated mice (Fig. 3), differences in the staining profiles of B220lo and B220hi populations suggested treatment-induced alteration of the constituent B lineage progenitor subpopulations. Further analysis of bone marrow cells with lymphocyte light-scatter characteristics indicated a twofold reduction in the percentage of CD43−B220+ cells in IFN-α2/α1–treated mice, whereas a twofold increase was observed in the percentage of CD43+B220+ (fractions A–C in the Hardy scheme, reference 9) cells (Fig. 4 A). When the CD43+B220+ population was analyzed for HSA expression, the percentage of CD43+B220+HSA+ cells (fractions B and C) was greatly decreased while the proportion of fraction A cells was increased (Fig. 4 B).


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 profile analysis of B lineage cells in the  bone marrow and spleen of PBS- and IFN-α2/α1–treated mice. Cells  were stained with FITC-conjugated anti-μ and Cy-chrome–labeled anti-B220 and the immunocytometric analysis was limited to cells with the  forward and side light scattering characteristics of lymphocytes. Percentages of IgM−B220+ and IgM+B220+ cells in the boxed areas are indicated.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Immunofluorescence profile analysis of B lineage cells in the bone marrow and spleen of PBS- and IFN-α2/α1–treated mice. Cells were stained with FITC-conjugated anti-μ and Cy-chrome–labeled anti-B220 and the immunocytometric analysis was limited to cells with the forward and side light scattering characteristics of lymphocytes. Percentages of IgM−B220+ and IgM+B220+ cells in the boxed areas are indicated.
Mentions: An ∼50% decrease in the percentage of B220+IgM+ B cells was observed for the bone marrow and splenic lymphocyte populations in the IFN-α2/α1–treated neonates (Fig. 3). Reductions in the absolute number of B cells were estimated to be 89 and 84% in the bone marrow and spleen, respectively. Although the percentage of residual B220+IgM− B lineage cells was only modestly decreased in the bone marrow of IFN-α2/α1–treated mice (Fig. 3), differences in the staining profiles of B220lo and B220hi populations suggested treatment-induced alteration of the constituent B lineage progenitor subpopulations. Further analysis of bone marrow cells with lymphocyte light-scatter characteristics indicated a twofold reduction in the percentage of CD43−B220+ cells in IFN-α2/α1–treated mice, whereas a twofold increase was observed in the percentage of CD43+B220+ (fractions A–C in the Hardy scheme, reference 9) cells (Fig. 4 A). When the CD43+B220+ population was analyzed for HSA expression, the percentage of CD43+B220+HSA+ cells (fractions B and C) was greatly decreased while the proportion of fraction A cells was increased (Fig. 4 B).

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