T cell regulation of interferon α/β (IFN-α/β) production by alloantigen-stimulated bone marrow cells

We have previously reported that mouse bone marrow cells produce high levels of interferon-α/β (IFN-α/β) after 5 to 6 days of in vitro culture with irradiated allogenic spleen cells. The current study was initiated to determine whether or not T cells are important for alloantigen-induced IFN-α/β production by mouse bone marrow cells. Bone marrow cells and spleen cells were obtained from C57BL/6 mice. These cells were treated with different monoclonal antisera and complement, and then were cultured 5 to 6 days with irradiated DBA spleen cells. The results from these experiments indicated that optimal IFN-α/β production by alloantigen-stimulated bone marrow cells required Lyt-1⁺2⁺ T cells. In addition, when bone marrow cells obtained from nu/nu B10 mice were cultured with alloantigen, only low levels of IFN were produced when compared with IFN production by bone marrow cells obtained from normal littermate B10 mice. The addition of nylon wool-enriched splenic T cells to cultures containing bone marrow cells and alloantigen resulted in an augmentation of IFN-α/β production by threefold to fivefold. Furthermore, bone marrow cells obtained from alloantigen-immunized mice produced much higher levels of IFN-α/β and in a shorter period of time (2 to 3 days) when compared with bone marrow cells obtained from control or nonimmunized mice. Cyclosporin A (CsA) has been shown to inhibit predominantly T cell-dependent responses. The effect of CsA on IFN production by alloantigen-stimulated bone marrow and spleen cells was investigated. The addition of CsA at concentrations as low as 0.1 μg/ml inhibited not only IFN-γ production by alloantigen-stimulated spleen cells, but also IFN-α/β production by alloantigen-stimulated bone marrow cells. In contrast, IFN-α/β production by Newcastle disease virus-infected spleen cells, bone marrow cells, or L cells was not inhibited by the addition of CsA (1 μg/ml). Thus, the ability of bone marrow cells to produce high levels of IFN-α/β after in vitro culture with alloantigen is dependent upon T cells resident in the bone marrow. IFN-α/β production by alloantigen-stimulated bone marrow cells may play a major role in the pathogenesis associated with graft-vs-host disease and in T cell regulation of hematopoiesis.