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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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IL-7 responses of bone marrow cells from PBS- and IFN-α2/α1–treated mice. Bone marrow cells were cultured with different  concentrations of IL-7 for 72 h, and pulsed with [3H]thymidine for the final 8 h. Results are shown as mean cpm (±SD) from triplicate or quadruplicate cultures.
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Figure 5: IL-7 responses of bone marrow cells from PBS- and IFN-α2/α1–treated mice. Bone marrow cells were cultured with different concentrations of IL-7 for 72 h, and pulsed with [3H]thymidine for the final 8 h. Results are shown as mean cpm (±SD) from triplicate or quadruplicate cultures.

Mentions: To examine the effects of IFN-α2/α1 treatment on pre-B and B cell response, bone marrow B cells were stimulated with LPS and IL-7 at different concentrations. The proliferative response of early B lineage cells to IL-7 was dramatically inhibited in mice treated with IFN-α2/α1 (Fig. 5), thus providing functional evidence for the early abortion of B lineage differentiation. Diminished LPS responsiveness was also observed for the bone marrow cells in treated mice (data not shown).


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

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

IL-7 responses of bone marrow cells from PBS- and IFN-α2/α1–treated mice. Bone marrow cells were cultured with different  concentrations of IL-7 for 72 h, and pulsed with [3H]thymidine for the final 8 h. Results are shown as mean cpm (±SD) from triplicate or quadruplicate cultures.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: IL-7 responses of bone marrow cells from PBS- and IFN-α2/α1–treated mice. Bone marrow cells were cultured with different concentrations of IL-7 for 72 h, and pulsed with [3H]thymidine for the final 8 h. Results are shown as mean cpm (±SD) from triplicate or quadruplicate cultures.
Mentions: To examine the effects of IFN-α2/α1 treatment on pre-B and B cell response, bone marrow B cells were stimulated with LPS and IL-7 at different concentrations. The proliferative response of early B lineage cells to IL-7 was dramatically inhibited in mice treated with IFN-α2/α1 (Fig. 5), thus providing functional evidence for the early abortion of B lineage differentiation. Diminished LPS responsiveness was also observed for the bone marrow cells in treated mice (data not shown).

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