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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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Enhanced Ly-6C antigen expression after IFN-α2/α1 treatment. 3-d-old mice received intraperitoneal injections of IFN-α2/α1 (4 ×  105 U) or PBS for 6 d, and viable cells from the indicated tissues were  stained with anti–Ly-6C antibody 1 d after the last injection. Thin lines  represent the staining patterns of cells from control mice; thick lines represent cells from IFN-α2/α1–treated mice.
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Figure 2: Enhanced Ly-6C antigen expression after IFN-α2/α1 treatment. 3-d-old mice received intraperitoneal injections of IFN-α2/α1 (4 × 105 U) or PBS for 6 d, and viable cells from the indicated tissues were stained with anti–Ly-6C antibody 1 d after the last injection. Thin lines represent the staining patterns of cells from control mice; thick lines represent cells from IFN-α2/α1–treated mice.

Mentions: The systemic effects of IFN-α/β were examined after a 6 d course of treatment initiated on the third day of life. When cells from the bone marrow, spleen, liver, and thymus were examined for Ly-6C expression, enhanced expression of Ly-6C was observed for all of the different cell types (Fig. 2), indicating a strong physiological response to the exogenous IFN-α2/α1 (37).


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

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

Enhanced Ly-6C antigen expression after IFN-α2/α1 treatment. 3-d-old mice received intraperitoneal injections of IFN-α2/α1 (4 ×  105 U) or PBS for 6 d, and viable cells from the indicated tissues were  stained with anti–Ly-6C antibody 1 d after the last injection. Thin lines  represent the staining patterns of cells from control mice; thick lines represent cells from IFN-α2/α1–treated mice.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Enhanced Ly-6C antigen expression after IFN-α2/α1 treatment. 3-d-old mice received intraperitoneal injections of IFN-α2/α1 (4 × 105 U) or PBS for 6 d, and viable cells from the indicated tissues were stained with anti–Ly-6C antibody 1 d after the last injection. Thin lines represent the staining patterns of cells from control mice; thick lines represent cells from IFN-α2/α1–treated mice.
Mentions: The systemic effects of IFN-α/β were examined after a 6 d course of treatment initiated on the third day of life. When cells from the bone marrow, spleen, liver, and thymus were examined for Ly-6C expression, enhanced expression of Ly-6C was observed for all of the different cell types (Fig. 2), indicating a strong physiological response to the exogenous IFN-α2/α1 (37).

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