Blockade of T- and B-lymphocyte development by antibody to the γc subunit of the receptors for interleukins 2, 4, and 7

Abstract

Cytokines are important regulators of hematopoesis. Mutations in γc, which is a subunit shared by the receptors for interleukin (IL) 2, IL-4, and IL-7, have been causally associated with human X chromosome-linked severe combined immunodeficiency disease. This finding indicates a mandatory role for cytokine receptor signaling at one or more stages of lymphocyte development. To evaluate the cellular level at which γc is critical for lymphopoiesis, the effect of monoclonal antibodies to γc on the capacity of syngeneic bone marrow cells to reconstitute the hematopoietic compartment of lethally irradiated recipient mice was examined. We show that monoclonal antibody to γc blocked lymphocyte development at or before the appearance of pro-B cells and prior to or at the seeding of the thymus by precursor cells while erythromyeloid cell development was normal. These results suggest that one level of lymphocyte development that requires γc is a point in hematopoietic cell differentiation near the divergence of lymphopoiesis and erythromyelopoesis.