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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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Recovery of T and B cell development after neonatal treatment with IFN-α2/α1. 3-d-old mice injected with PBS or IFN-α2/α1  for 6 consecutive d were examined serially after the last treatment. T and  B cells were identified by CD3 and B220 expression, respectively. Results  of the enumeration of thymocytes, T cells in the spleen, and B cells in the  spleen and bone marrow are presented as mean percentages of control  values (I = ± standard error; n = 3 mice).
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Figure 7: Recovery of T and B cell development after neonatal treatment with IFN-α2/α1. 3-d-old mice injected with PBS or IFN-α2/α1 for 6 consecutive d were examined serially after the last treatment. T and B cells were identified by CD3 and B220 expression, respectively. Results of the enumeration of thymocytes, T cells in the spleen, and B cells in the spleen and bone marrow are presented as mean percentages of control values (I = ± standard error; n = 3 mice).

Mentions: When T and B cell development was examined as a function of time after discontinuation of the IFN-α2/α1 treatment, no recovery was observed for the T lineage cells in the thymus and spleen or of the B lineage cells in the bone marrow and spleen in the first week after the 6 d course of interferon therapy (Fig. 7). However, by 2 wk after the final injection, mice treated with IFN-α2/ α1 showed significant signs of recovery as reflected by an increase in T and B cell numbers in the thymus, bone marrow, and spleen. By 1 mo after the neonatal treatment, the mice appeared to recover from the effects of the IFN-α2/ α1 in terms of T and B cell numbers.


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

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

Recovery of T and B cell development after neonatal treatment with IFN-α2/α1. 3-d-old mice injected with PBS or IFN-α2/α1  for 6 consecutive d were examined serially after the last treatment. T and  B cells were identified by CD3 and B220 expression, respectively. Results  of the enumeration of thymocytes, T cells in the spleen, and B cells in the  spleen and bone marrow are presented as mean percentages of control  values (I = ± standard error; n = 3 mice).
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Related In: Results  -  Collection

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Figure 7: Recovery of T and B cell development after neonatal treatment with IFN-α2/α1. 3-d-old mice injected with PBS or IFN-α2/α1 for 6 consecutive d were examined serially after the last treatment. T and B cells were identified by CD3 and B220 expression, respectively. Results of the enumeration of thymocytes, T cells in the spleen, and B cells in the spleen and bone marrow are presented as mean percentages of control values (I = ± standard error; n = 3 mice).
Mentions: When T and B cell development was examined as a function of time after discontinuation of the IFN-α2/α1 treatment, no recovery was observed for the T lineage cells in the thymus and spleen or of the B lineage cells in the bone marrow and spleen in the first week after the 6 d course of interferon therapy (Fig. 7). However, by 2 wk after the final injection, mice treated with IFN-α2/ α1 showed significant signs of recovery as reflected by an increase in T and B cell numbers in the thymus, bone marrow, and spleen. By 1 mo after the neonatal treatment, the mice appeared to recover from the effects of the IFN-α2/ α1 in terms of T and B cell numbers.

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