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J. Exp. Med.,
Volume 188, Number 2, July 20, 1998 409-414
By
*
From the * Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville
3050, Victoria, Australia; and Naive T cells recirculate mainly within the secondary lymphoid compartment, but once activated they can enter peripheral tissues and perform effector functions. To activate naive T cells,
foreign antigens must traffic from the site of infection to the draining lymph nodes, where they
can be presented by professional antigen presenting cells. For major histocompatibility complex
class I-restricted presentation to CD8+ T cells, this can occur via the cross-presentation pathway. Here, we investigated the conditions allowing antigen access to this pathway. We show
that the level of antigen expressed by peripheral tissues must be relatively high to facilitate
cross-presentation to naive CD8+ T cells. Below this level, peripheral antigens did not stimulate by cross-presentation and were ignored by naive CD8+ T cells, although they could sensitize tissue cells for destruction by activated cytotoxic T lymphocytes (CTLs). Interestingly,
CTL-mediated tissue destruction facilitated cross-presentation of low dose antigens for activation of naive CD8+ T cells. This represents the first in vivo evidence that cellular destruction
can enhance access of exogenous antigens to the cross-presentation pathway. These data indicate that the cross-presentation pathway focuses on high dose antigens and those released during tissue destruction.
The Department of Pathology and Immunology, Monash Medical
School, Prahran 3181, Victoria, Australia
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