The Thymus and T Cell Trafficking

The thymus is generally not considered to be a sight of immune activation. Based on the classic studies of Gowans, traffic of lymphocytes was unidirectional, i.e., out of the thymus into the blood and peripheral lymphoid organs (Gowans and Knight, 1964). However, there is evidence that small numbers of peripheral immunocompetent T cells migrate to the thymus, entering via the medulla (Naparstek et al, 1982, 1993; Michie et al., 1988; Agus et al, 1991). Most of the thymic immigrants are T cells activated in the peripheral immune system with an even smaller contribution made by resting T cells (Michie et al., 1988; Agus et al., 1991; Naparstek et al, 1993). It is not known if the rate or number of thymic immigrants is increased by an inflammatory reaction in the thymus. Likewise, it is not known if self-reactive T cell immigrants are activated if they encounter their specific antigens in the thymus. Thymus T cell immigrants specific for the lym-phocytic choriomeningitis virus (LCMV) clear infectious foci from the thymus (Hirokawa et al., 1989; Gossmann et al., 1991; King et al., 1992). Therefore, peripheral T cells can be activated when they engage specific foreign antigens in the thymus. When self-reactive T cells encounter their antigens in other compartments in the presence of required costimulatory signals, they can be activated to express their differentiation program (Mondino et al., 1996). One mechanism that leads to a milieu that promotes the abrogation of tolerance peripherally is infection. Local infection can lead to the upregulation of MHC antigens and costimu-latory molecules on cells that express low levels of self-antigens and, thereby, to activation of autoreactive T cells (Mondino et al., 1996).

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