Different mechanisms regulate CD4(+) T cell independent induction of oral and nasal tolerance of CD8(+) T cells

作者：van den Berg Hendrik; Greuter Mascha; Kraal Georg; den Haan Joke M M^*

来源：Immunobiology, 2010, 215(2): 163-171.

DOI：10.1016/j.imbio.2009.01.012

• Mucosal tolerance
• Regulatory T cell
• CD8(+) T cell
• CD4(+) T cell
• Suppression

Mucosal administration of antigens is known to induce antigen specific regulatory CD4(+) T cells, but less is known about the effects on CD8(+) T cell function. Using a murine model for mucosal tolerance induction, we show that both oral and nasal OVA (ovalbumin) application reduced OVA specific CD8(+) T effector cell numbers and suppressed in vivo cytotoxicity in response to subsequent immunisation. To investigate whether CD4(+) T cells are essential for oral or nasal CD8(+) T cell tolerance, we used MHC class 11 deficient mice. Normal CD8(+) T cell tolerance was observed in MHC class 11 deficient mice, indicating that CD4(+) T cells are not required for both oral and nasal CD8(+) T cell tolerance induction. To study the direct effects of mucosal antigen application on naive CD8(+) T cells, we adoptively transferred OVA specific transgenic CD8(+) T cells and analysed their fate after mucosal antigen application. Oral OVA application reduced the numbers of OVA specific CD8(+) T cells, whereas nasal OVA application induced proliferation. However, the expanded population of OVA specific CD8(+) T cells from nasally treated mice was unable to proliferate upon re-stimulation, In conclusion, our studies point to suppressive effects of the mucosal immune system directly on CD8(+) T cells and indicate multiple mechanisms of tolerance induction. More insight in these mechanisms of tolerance induction is necessary for the development of mucosal tolerance therapies for autoimmune diseases and allergy.

• 出版日期2010-2