Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172

Mycobacterium tuberculosis (tubercle bacilli) and the related acid-fast bacteria including Mycobacterium bovis Bacille Calmett-Guerin (BCG) have a characteristic cell wall (CW) containing various lipoglycans and glycolipids. Such lipoglycans have been reported to activate type-I inflammatory responses via dendritic cells (DCs) through Toll-like receptor 2. In this study, lipoglycans, lipoarabinomannan (LAM), lipomannan (LM) and phosphatidylinositol mannoside (PIM), were purified from the CW fractions of M. bovis BCG Tokyo-172, and the effect on the differentiation of human peripheral blood naive CD4 T cells into T h 1 and T h 2 was examined. LAM/LM molecules enhanced T h 1 differentiation under both T h 1 and T h 2 conditions, whereas some other glycolipids and phospholipid enhanced T h 2 differentiation under T h 2 conditions. Other components had little effect under the given conditions. Even in highly purified CD4 T cell cultures, LAM/LM enhanced T h 1 generation only under T h 1 culture conditions. These results indicate that LAM/LM possesses a potent augmenting activity in T h 1 differentiation in human CD4 T cells. LAM/LM appeared to act directly on naive CD4 T cells to enhance T h 1 differentiation under T h 1 culture conditions, while acting indirectly to up-regulate the generation of T h 1 cells via IL-12/DCs under T h 1 and T h 2 conditions. Therefore, these results provide the first evidence indicating that LAM/LM from M. bovis BCG may possess a potent modulating activity in the human system, and thus supporting the strategy for the use of BCG components in the vaccine development for such T h 2 diseases as allergic asthma and rhinitis.