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Brief Definitive Reports

Christian Kurts^,*, Jacques F.A.P. Miller^*, Rathan M. Subramaniam^*, Francis R. Carbone, and William R. Heath^*

From the ^* Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia; and The Department of Pathology and Immunology, Monash Medical School, Prahran 3181, Victoria, Australia

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.

Key Words: CD8⁺ T lymphocytes • T cell activation • antigen presentation • antigen presenting cells • apoptosis

C. Kurts is supported by a fellowship from the Deutsche Forschungsgemeinschaft (Grant Ku1063/1-2). This work was funded by National Institutes of Health grant AI-29385 and grants from the National Health and Medical Research Council of Australia and the Australian Research Council.

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