J. Exp. Med., Volume 187, Number 1, January 5, 1998 79-87

Impairment of  T and B Cell Development by Treatment with a Type I Interferon

By Qun Lin,^* Chen Dong,^* and Max D. Cooper^*

From the ^* Division of Developmental and Clinical Immunology, the Department of Medicine, the Department of Pediatrics, and the Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294; and the  Howard Hughes Medical Institute, Birmingham, Alabama 35294

Type I interferons  and , 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-2/1 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-2/1-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-/ receptor^/ mice, T and B cell development were unaffected by the IFN-2/1 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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