In Brief

Mucosal immunology

Induction of colonic regulatory T cells by indigenous Clostridium species Atarashi, K. et al. Science 23 Dec 2010 (doi: 10.1126/science.1198469)

There is currently much interest in the crosstalk between the gut microbiota and the immune system. This study shows that forkhead box P3 (FOXP3)⁺ regulatory T (T_Reg) cells are most abundant in the colon and, through the use of germ-free or antibiotic-treated specific pathogen-free (SPF) mice, that accumulation of these cells after weaning depends on the gut microbiota. Further analysis identified Clostridium spp. belonging to clusters IV and XIV as the specific component of the microbiota that induces colonic T_Reg cell accumulation. A defined mix of Clostridium spp. induced the production of transforming growth factor-β by intestinal epithelial cells (in a TLR-, NOD- and dectin 1-independent manner) and the accumulation of IL-10⁺CTLA4^hi T_Reg cells in the colon. Finally, oral inoculation of neonatal SPF mice with Clostridium spp. suppressed the development of DSS-induced colitis and systemic IgE responses.

Dendritic cells

Mucosal and systemic anti-HIV immunity controlled by A20 in mouse dendritic cells Hong, B. et al. J. Clin. Invest. 4 Jan 2011 (doi: 10.1172/JCI42656)

The ubiquitin-modifying enzyme A20 (also known as TNFAIP3) is a negative feedback regulator of several important pro-inflammatory signalling pathways and controls the immunostimulatory function of antigen-presenting cells. Silencing of A20 mRNA may therefore affect the potency of dendritic cells (DCs) in the induction of HIV-specific immune responses. Injection of mice with A20-silenced, bone-marrow-derived DCs loaded with recombinant HIV envelope protein gp120 resulted in cellular and humoral gp120-specific immune responses, both in mucosal tissues and systemically. These DCs migrated more efficiently to the mesenteric lymph nodes than control DCs and induced the expression of gut-homing receptors on activated lymphocytes, partly through the production of retinoic acid. Furthermore, A20-silenced gp120-pulsed DCs enhanced cytotoxic T cell responses in the absence of CD4⁺ T cells. So, silencing of A20 may enhance the efficacy of DC-based vaccines against HIV.

Tumour immunology

CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens Asano, K. et al. Immunity 30 Dec 2010 (doi: 10.1016/j.immuni.2010.12.011)

It is not known how antigen-presenting cells in the lymph node internalize and cross-present tumour-associated antigens to CD8⁺ T cells for the initiation of effective antitumour cytotoxic T lymphocyte (CTL) responses. In agreement with previous observations, subcutaneous injection of dead tumour cells activated tumour-specific CTLs. However, this did not induce the migration of CD11c⁺ DCs from the skin to the draining lymph node; instead, the dead cells travelled via lymphatic flow to the draining lymph node, where they were phagocytosed by CD169⁺ macrophages in a phosphatidylserine-dependent manner. Antitumour responses did not develop when dead tumour cells were administered to tumour-bearing mice that lacked CD169⁺ macrophages. Finally, CD11c⁺CD169⁺ macrophages (which mainly localized in the cortical and paracortical sinus) were shown to directly cross-present dead-cell-associated antigen to CD8⁺ T cells. So, CD169⁺ macrophages promote tumour immunity following tumour cell death.