Cross-priming with an epicutaneously introduced soluble protein antigen generates Tc1 cells

Epicutaneous sensitization with a protein antigen was demonstrated to induce a predominant type 2 CD4 T cell response with high IgE production in mice. On the other hand, its CD8 T cell responses have not been addressed probably partly because of the generally accepted concept that cross-priming of soluble protein is an inefficient process. Here, we used an established patch-applied murine model to demonstrate that cross-priming with an epicutaneously introduced soluble protein antigen, though inefficient, generated mainly Tc1 cells, but not Tc2 cells. In the presence of an irritant or hapten, the efficiency of this cross-priming process could be enhanced and more Tc1 cells were generated. CpG oligonucleotides also promote the generation of Tc1 cells. In contrast, lipopolysaccharide and poly (inosinic-cytidylic) acid [poly (I:C)] have no effect. Together, these results provide supportive evidence of the epicutaneous sensitization of human cutaneous lymphocyte-associated antigen-positive CD8 T cells found in the peripheral blood or tissues of patients. The surprising observation of the type 1 character of the generated CD8 T cells will also help us to better understand the complicated pathogenesis of atopic and cutaneous inflammatory diseases.