The adaptation model of immunity: Is the goal of central tolerance to eliminate defective T cells or self‐reactive T cells?

The self‐non‐self model and the danger model are designed to understand how an immune response is induced. These models are not meant to predict if an immune response may succeed or fail in destroying/controlling its target. However, these immunological models rely on either self‐antigens or self‐dendritic cells for understanding of central tolerance, which have been discussed by Fuchs and Matzinger in response to Al‐Yassin. In an attempt to address some questions that these models are facing when it comes to understanding central tolerance, I propose that the goal of negative selection in the thymus is to eliminate defective T cells but not self‐reactive T cells. Therefore, any escape from negative selection could increase lymphopenia because of the depletion of defective naïve T cells outside the thymus, as seen in the elderly.