Lin Q, Dong C, Cooper M D
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
J Exp Med. 1998 Jan 5;187(1):79-87. doi: 10.1084/jem.187.1.79.
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.
I型干扰素α和β是细胞生长和分化的天然调节因子，已被证明在体外可抑制IL-7诱导的B细胞前体的生长和存活。在体外实验中证实其对B淋巴细胞生成有抑制作用后，我们用一种活性IFN-α2/α1杂合分子处理新生小鼠，以评估其在体内调节B细胞和T细胞发育的潜力。经IFN-α2/α1处理的小鼠骨髓和脾脏细胞数量大幅减少，B谱系细胞减少超过80%。CD43+B220+HSA-细胞的骨髓祖细胞群体未受影响，但CD19+前B细胞及其B谱系后代的发育严重受损。相应地，干扰素处理几乎消除了骨髓中对IL-7有反应的细胞。处理后的小鼠胸腺细胞数量也减少了80%以上。对残留胸腺细胞的表型分析表明，抑制作用发生在T细胞分化的前T细胞阶段。在IFN-α/β受体缺陷小鼠中，T细胞和B细胞发育不受IFN-α2/α1处理的影响。数据表明，I型干扰素可通过对抗关键的IL-7反应来可逆地抑制早期T细胞和B细胞发育。
