Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation

Abstract

Organ-specific autoimmune diseases may be induced by infiltration of the target tissue by CD4(+) T cells with specificity for self antigen(s). As disease progresses, T cells of other specificities appear in the tissue. Traffic of naive, antigen-inexperienced T cells to target tissues has not been shown, although many studies have shown extravasation of activated or memory T cells. We have used a novel experimental system to track naive T cells to the central nervous system (CNS) in TCR transgenic mice with adoptively transferred experimental autoimmune encephalomyelitis. Ovalbumin (OVA)-specific CD4(+) T cells were equivalent in number to disease-inducing myelin basic protein (MBP)-specific T cells at disease onset. Furthermore, OVA-specific T cells retained a naive phenotype and did not transcribe Th1 cytokines, in contrast to MBP-specific T cells. These findings demonstrate that the T cell pool in the CNS of animals with demyelinating disease contains potential recruits from the time of disease onset, and that T cells require more than an inflammatory milieu for their induction to the autoimmune attack.