J. Exp. Med., Volume 186, Number 12, December 15, 1997 2057-2062

BRIEF DEFINITIVE REPORT:
CD4⁺ T Cell Help Impairs CD8⁺ T Cell Deletion Induced by Cross-presentation of Self-Antigens and Favors Autoimmunity

By Christian Kurts,^* Francis R. Carbone, Megan Barnden, Effrossini Blanas,^* Janette Allison,^* William R. Heath,^* and Jacques F.A.P. Miller^*

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

Self-antigens expressed in extrathymic tissues such as the pancreas can be transported to draining lymph nodes and presented in a class I-restricted manner by bone marrow-derived antigen-presenting cells. Such cross-presentation of self-antigens leads to CD8⁺ T cell tolerance induction via deletion. In this report, we investigate the influence of CD4⁺ T cell help on this process. Small numbers of autoreactive OVA-specific CD8⁺ T cells were unable to cause diabetes when adoptively transferred into mice expressing ovalbumin in the pancreatic  cells. Coinjection of OVA-specific CD4⁺ helper T cells, however, led to diabetes in a large proportion of mice (68%), suggesting that provision of help favored induction of autoimmunity. Analysis of the fate of CD8⁺ T cells indicated that CD4⁺ T cell help impaired their deletion. These data indicate that control of such help is critical for the maintenance of CD8⁺ T cell tolerance induced by cross-presentation.

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