BACILLUS-CALMETTE-GUERIN SEQUESTERED IN THE BRAIN PARENCHYMA ESCAPES IMMUNE RECOGNITION

We have previously shown that heat-killed bacillus Calmette-Guerin (BC G) injected into the brain parenchyma becomes sequestered behind the b lood-brain barrier for months, apparently unrecognised by the immune s ystem (Matyszak and Ferry, 1995, 1996a,b). In this paper we have studi ed T-cell and antibody responses to purified protein derivative (PPD) at different times after intracranial injection of BCG or after the sa me dose of BCG was injected intradermally. We detected no antibody to PPD in the sera of animals which received intracranial injection, alth ough there was a clear antibody response in the sera of animals inject ed intradermally, as shown using immunoblot analysis. The skin contact sensitivity to PPD was robust in animals which had received a previou s intradermal injection of BCG. 72 h after a PPD injection, the inject ed site showed many MHC class II + macrophages and T-cells. However, t he response in skin following PPD challenge, in animals injected intra cranially (i.c.), was comparable with that of naive animals which had received no previous BCG challenge. The skin lesions in animals inject ed i.c. and in naive animals, were characterised by a small number of MHC class II + cells and rare T-cells. T-cell responses were also stud ied in an in vitro proliferation assay. The proliferative response was measured for cells isolated from the cervical lymph nodes and the spl een. Cells purified from the spleen and the cervical lymph nodes of an imals injected with BCG i.c. showed no specific proliferative response to PPD. The response was comparable to that found in naive, uninjecte d animals. However, spleen and cervical lymph node cells from animals injected intradermally with BCG showed a significant proliferative res ponse to PPD. These results show that a dose of bacteria injected into the brain parenchyma fails to prime the immune system even though the same dose injected subcutaneously will do so. This response to bacter ia in the CNS differs from that previously reported for soluble protei ns. (C) 1998 Elsevier Science B.V.