TY - JOUR
T1 - Impairment of T and B cell development by treatment with a type I interferon
AU - Lin, Qun
AU - Dong, Chen
AU - Cooper, Max D.
PY - 1998/1/5
Y1 - 1998/1/5
N2 - Type 1 interferons α and β, naturally produced regulators of cell growth and differentiation, have been shown to inhibit IL-7-induced growth and survival or 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-α2/α1 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-α2/α1-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-α/β receptor(-/-) mice, T and B cell development were unaffected by the IFN- α2/α1 treatment. The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.
AB - Type 1 interferons α and β, naturally produced regulators of cell growth and differentiation, have been shown to inhibit IL-7-induced growth and survival or 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-α2/α1 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-α2/α1-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-α/β receptor(-/-) mice, T and B cell development were unaffected by the IFN- α2/α1 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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U2 - 10.1084/jem.187.1.79
DO - 10.1084/jem.187.1.79
M3 - Article
C2 - 9419213
AN - SCOPUS:0031962665
SN - 0022-1007
VL - 187
SP - 79
EP - 87
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -