Visualization of antigen-specific T cell activation in vivo in response tointracerebral administration of a xenopeptide

Allogeneic or xenogenic tissues exhibit prolonged survival when grafted int o the brain parenchyma in comparison to grafting into peripheral sites. The brain, therefore, has long been considered an immunologically privileged s ite. However, the immunological privilege of the brain is not absolute, and it cannot shield neural xenografts from rejection. In our laboratory, we a re interested in determining how to prevent neural xenograft rejection. To do so, we need to first understand how the immune system responds to CNS an tigens leading to graft rejection. In order to monitor immune system respon ses to CNS antigens an adoptive transfer system was used to directly track CNS antigen-specific CD4(+) T cell responses in vivo. This would then allow us to monitor changes in the number, activation state, and anatomic distri bution of antigen-specific cells. We have found that, after intracerebral i njection of xeno peptide antigens with adjuvant, antigen-specific cells acc umulated in the cervical lymph node, proliferated there for several days, a nd then disappeared slowly from the nodes. Interestingly, peptide antigens given intracerebrally also stimulated a strong antigen-specific CD4(+) T ce ll response. Moreover, cells remaining in the lymph node 8 days after antig en stimulation produce IL-2 with secondary antigenic challenge. Previous st udies have shown that the administration of antigens without adjuvant in a monomeric form via either the intraperitoneal or intravenous route has fail ed to induce cell-mediated immunity and resulted in antigen-specific T cell unresponsiveness. Our findings demonstrate that antigen delivered intracer ebrally can activate immune responses in a manner different than antigen de livered to peripheral sites outside of the CNS. (C) 2000 Academic Press.