Development and maturation of Langerhans cells, spleen and bone marrow dendritic cells in TNF-alpha/lymphotoxin-alpha double-deficient mice.

Dendritic cells are key regulators of immunity and tolerance. TNF-alpha has manifold effects on dendritic cells. It is an indispensable ingredient in several dendritic cell generation protocols, especially in the human, and it is included in diverse maturation stimuli for dendritic cells. Mice deficient in various components of the TNF/lymphotoxin system (TNF-alpha, lymphotoxin-alpha and -beta, TNF receptors, combinations thereof) have profound defects in mounting immune responses to infections. The dendritic cell system in these mice has been incompletely studied to date. We therefore investigated dendritic cells from the epidermis (Langerhans cells), spleen and the bone marrow of mice double-deficient in TNF-alpha and lymphotoxin-alpha. We report that dendritic cells in these mice are grossly normal. Langerhans cells, spleen and bone marrow dendritic cells can develop and mature. Their expression of MHC II and CD86 is not impaired, and their T cell-stimulatory as well as antigen-processing capacity is comparable to their normal counterparts. Thus, the described defects in these mice appear to be due the lack of lymph nodes, the disturbed architecture of the spleen, and deranged chemokine production patterns, rather than to a profoundly altered dendritic cell system.