A comparison of leucocyte responses to heat-killed bacillus Calmette-Guérin in different CNS compartments

We have previously shown that heat-killed bacillus Calmette-Guérin (BCG) injected into the CNS parenchyma does not produce a typical delayed-type hypersensitivity (DTH) response [23]. In this paper we have compared the initial leucocyte response in the CNS parenchyma, ventricles and skin to gain insight into the mechanisms by which the DTH response in the CNS might be controlled. We have found that 10(5) organisms of heat-killed BCG injected into either the CNS parenchyma or the lateral ventricles produced a rapid neutrophil response at the site of the injection, which was comparable with that in the skin. The neutrophil response resolved within the first week. Unlike the neutrophil response, the mononuclear phagocyte response in the CNS parenchyma was much smaller than that seen in the ventricles and the skin and it resolved within 4 weeks. Furthermore, the myelomonocytic response in the CNS parenchyma failed to clear the BCG. The acute inflammatory response in the choroid plexus/ventricles and skin developed with a similar time-course into a typical DTH response. After the first week, lesions at these two sites were composed predominantly of T-cells and macrophages. DTH lesions were still detected at both sites after 6 weeks. The failure of the immune system to recognize foreign antigens sequestrated in the CNS parenchyma may have significant implications especially in studies of inflammatory responses in the CNS of unknown origin.