TH17 cells thrive and react to the OVA antigen in mice lacking CD11b.

According to dogma, APCs that have only few costimulatory receptors dampen immunity. These APCs can't give T cells the stimulatory boost they need to become offensive. But some APCs with lots of costimulatory receptors can somehow still keep T cells in low gear.

One APC receptor that might direct this alternative pathway, the authors hypothesized, is CD11b. Mice need this integrin to remove neutrophils and macrophages from infection sites and subdue inflammation. CD11b deficiency also worsens autoimmunity, suggesting that the receptor might enable the immune system to tolerate certain antigens.

The authors studied the effect of CD11b on tolerance by feeding normal and CD11b-deficient mice low doses of ovalbumin (OVA) for a week and then challenging them with high doses of this antigen. The CD11b-deficient mice failed this tolerance test and generated high levels of OVA-specific T cells. Tolerance was restored, however, when these mice were supplied with APCs from normal mice.

The CD11b-deficient mice had high levels of two cytokines, IL-6 and IL-23, which support the growth of Th17 cells, a T cell subset that is associated with allergies and autoimmunity. The mutant mice had almost three times the normal numbers of Th17 cells, suggesting that CD11b suppresses the growth of this dangerous T cell subset and thereby establishes tolerance.

The authors are now investigating whether CD11b signaling directly blocks IL-6/IL-23 production and whether a particular APC subset requires CD11b expression to prevent the development of Th17 cells.

Related Article

CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation

Driss Ehirchiou, Ying Xiong, Guangwu Xu, Wanjun Chen, Yufang Shi, and Li Zhang
J. Exp. Med. 2007 204: 1519-1524. [Abstract] [Full Text] [PDF]