Mouse CD11bhigh lung dendritic cells have more potent capability to induce IgA than CD103+ lung dendritic cells in vitro.

Lung dendritic cells (LDCs) are primary antigen-presenting cells that develop IgA-producing plasma cells in the lung through class switch recombination (CSR) in naive B cells. Recently, the major LDC subsets were found to comprise CD103(-)CD11b(high) LDCs (CD11b(high) LDCs) and CD103(+)CD11b(low or negative) LDCs (CD103(+) LDCs), but their abilities to induce IgA production have not been defined. Under T cell-dependent (T-D) and T cell-independent (T-ID) conditions, we compared the abilities of these two LDC populations to induce IgA. CD11b(high) or CD103(+) LDCs obtained from BALB/c mice were cocultured with naive IgD(+) B cells in the presence of LPS, with or without anti-CD40 monoclonal antibody (mAb) (i.e., T-D and T-ID coculture conditions, respectively). Under both T-D and T-ID conditions, CD11b(high) LDCs induced significantly greater amounts of IgA production, together with a significantly higher mRNA expression of activation-induced cytidine deaminase, than did CD103(+) LDCs. However, the protein expression of a proliferation-inducing ligand, B cell-activating factor of the tumor necrosis family, or retinaldehyde dehydrogenase-1 did not differ between the two LDC subsets. CD11b(high) LDCs displayed a significantly greater capacity to secrete IL-6 and IL-10 in response to LPS, with or without anti-CD40 mAb. Moreover, the IgA production induced by CD11b(high) LDCs in T-D coculture was attenuated by neutralizing both IL-6 and IL-10. These findings suggest that, of the two major LDCs, CD11b(high) LDCs more efficiently induce IgA than do CD103(+) LDCs, possibly through their potent capacity to produce IgA-inducing cytokines.

Serum activity of indoleamine 2,3-dioxygenase predicts prognosis of community-acquired pneumonia.

OBJECTIVES: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. By depleting Trp, IDO plays a critical role in inducing immune suppression and tolerance. The aim of present study was to investigate serum IDO activity, determined by Kyn-to-Trp ratio (Kyn/Trp ratio), in community-acquired pneumonia (CAP) and to examine its clinical significance. METHODS: This study subjects consisted of 129 consecutive patients with CAP and 64 healthy controls. The concentrations of Kyn and Trp were measured simultaneously by liquid chromatography/electrospray ionization tandem mass spectrometry. RESULTS: The CAP patients had significantly higher Kyn concentrations and significant lower Trp concentrations than the controls (p < 0.0001 and p < 0.0001, respectively). Accordingly, IDO activity was significantly higher (2.4-fold) in the patients than in the controls (p < 0.0001). IDO activity correlated well with PSI (Pneumonia Severity Index) and CURB65 (p = 0.0005 and p < 0.0001, respectively). Moreover, the IDO activity and Kyn concentration were significantly higher in the nonsurvivors and were found to predict mortality in multivariate analysis. CONCLUSIONS: IDO activity was increased in CAP, and this activity was associated with the severity and outcome of this disease. These results suggest that IDO activity can predict prognosis of CAP.