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CD4⁺ Th1 and CD8⁺ Type 1 Cytotoxic T Cells Both Play a Crucial Role in the Full Development of Contact Hypersensitivity¹

Binghe Wang^*, Hiroshi Fujisawa, Lihua Zhuang^*, Irwin Freed^*, Brandon G. Howell^*, Shabana Shahid^*, Gulnar M. Shivji^*, Tak W. Mak and Daniel N. Sauder^2,*

^* Division of Dermatology, Sunnybrook and Women’s College Health Science Centre, and Amgen Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada; and Department of Dermatology, University of Tsukuba, Tsukuba, Ibaraki, Japan

The role of CD4⁺ vs CD8⁺ T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4⁺ or CD8⁺ T cells to directly address this issue. Mice lacking either CD4⁺ or CD8⁺ T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice. The depression of CHS was more significant in CD8 KO mice than in CD4 KO mice. Furthermore, in vivo depletion of either CD8⁺ T cells from CD4 KO mice or CD4⁺ T cells from CD8 KO mice virtually abolished CHS responses. Lymph node cells (LNCs) from hapten-sensitized CD4 and CD8 KO mice showed a decreased capacity for transferring CHS. In vitro depletion of either CD4⁺ T cells from CD8 KO LNCs or CD8⁺ T cells from CD4 KO LNCs resulted in a complete loss of CHS transfer. LNCs from CD4 and CD8 KO mice produced significant amounts of IFN-, indicating that both CD4⁺ and CD8⁺ T cells are able to secrete IFN-. LNCs from CD8, but not CD4, KO mice were able to produce IL-4 and IL-10, suggesting that IL-4 and IL-10 are mainly derived from CD4⁺ T cells. Intracellular cytokine staining of LNCs confirmed that IFN--positive cells consisted of CD4⁺ (Th1) and CD8⁺ (type 1 cytotoxic T) T cells, whereas IL-10-positive cells were exclusively CD4⁺ (Th2) T cells. Collectively, these results suggest that both CD4⁺ Th1 and CD8⁺ type 1 cytotoxic T cells are crucial effector cells in CHS responses to dinitrofluorobenzene and oxazolone in C57BL/6 mice.

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