Autoimmunity stimulated by adoptively transferred dendriticis cells is initiated by both alpha beta and gamma delta T cells but does not require MyD88 signaling

作者：Martin David A; Zhang Kang; Kenkel Justin; Hughes Grant; Clark Edward; Davidson Anne; Elkon Keith B^*

来源：The Journal of Immunology, 2007, 179(9): 5819-5828.

Vaccination of nonautoimmune prone mice with syngeneic dendritic cells (DC) readily induces anti-DNA autoantibodies but does not trigger systemic disease. We observed that anti-DNA autoantibody generation absolutely required e(3 T cells and that gamma delta T cells also contributed to the response, but that regulatory T cells restrained autoantibody production. Although both NZB/W F-1 mice and DC vaccinated C57/13L6 mice produced autoantibodies against dsDNA, vaccinated mice had higher levels of Abs against H1 histone and lower levels of antinucleosome Abs than NZB/W F, mice. Despite a 100-fold increase in IL-12 and Th1 skewing to a foreign Ag, OVA, synergistic TLR activation of DC in vitro failed to augment anti-DNA Abs or promote class switching beyond that induced by LPS alone. TLR stimulation was not absolutely required for the initial loss of B cell tolerance because anti-DNA levels were similar when wild-type (WT) or MyD88-deficient DC were used for vaccination or WT and MyD88-deficient recipients were vaccinated with WT DC. In contrast, systemic administration of LPS, augmented anti-DNA Ab levels and pro-, moted class switching, and this response was dependent on donor DC signaling via MyD88. LPS also augmented responses in the MyD88-deficient recipients, suggesting that LPS likely exerts its effects on both transferred DC and host B cells in vivo. These results indicate that both the alpha beta and gamma delta subsets are necessary for promoting autoantibody production by DC vaccination, and that although TLR/MyD88 signaling is not absolutely required for initiation, this pathway does promote augmentation, and Th1-mediated skewing, of anti-DNA autoantibodies.

• 出版日期2007-11-1
• 单位河北医科大学