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

Allogeneic or xenogenic tissues exhibit prolonged survival when grafted into the brain parenchyma in comparison to grafting into peripheral sites. The brain, therefore, has long been considered an immunologically privileged site. However, the immunological privilege of the brain is not absolute, and it cannot shield neural xenografts from rejection. In our laboratory, we are interested in determining how to prevent neural xenograft rejection. To do so, we need to first understand how the immune system responds to CNS antigens leading to graft rejection. In order to monitor immune system responses 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 distribution of antigen-specific cells. We have found that, after intracerebral injection of xeno peptide antigens with adjuvant, antigen-specific cells accumulated in the cervical lymph node, proliferated there for several days, and then disappeared slowly from the nodes. Interestingly, peptide antigens given intracerebrally also stimulated a strong antigen-specific CD4⁺ T cell response. Moreover, cells remaining in the lymph node 8 days after antigen stimulation produce IL-2 with secondary antigenic challenge. Previous studies have shown that the administration of antigens without adjuvant in a monomeric form via either the intraperitoneal or intravenous route has failed to induce cell-mediated immunity and resulted in antigen-specific T cell unresponsiveness. Our findings demonstrate that antigen delivered intracerebrally can activate immune responses in a manner different than antigen delivered to peripheral sites outside of the CNS.