- Kline JN,
- Waldschmidt TJ,
- Businga TR,
- et al.
Asthmatics and allergic patients have a surplus of Th-2 T-cells, which are responsible for the production of cytokines that drive the allergic and asthmatic states. Nonallergic, nonasthmatics do not routinely demonstrate a Th-2 profile. Because all children with normal immunity produce Th-1 T-cells, necessary for immune responsiveness to bacterial and viral antigens, it has been speculated that allergic children may somehow be more geared to a Th-2 T-cell pool. If true, the exposure of native infection diminished by immunization and hygiene may make children in industrialized nations more apt to produce Th-2. Bacterial DNA contains generous numbers of unmethylated CpG dinucleotides (CpG ODN) when compared with mammalian cells. These CpG motifs drive a Th-1 response. If allergic children in industrialized nations are not exposed to as many infections, their Th-1 response may be blunted allowing for a Th-2 overproduction.
Mice were sensitized to parasite protein and their allergic response was measured by airway eosinophilia, Th-2 cytokine induction, immunoglobulin E (IgE) production, and bronchial hyperreactivity. In other parasite-sensitized mice the CpG ODN was given at the same time as the parasite. Appropriate controls were included.
Mice exposed to parasite protein developed all the characteristics of asthma, including increased IgE, airway hyperreactivity, increased lung IL-4, and lung eosinophilia. In those mice who received parasite and CpG ODN none of the characteristics of asthma developed. The mice who received CpG ODN also produced more interferon-gamma and IL-12, both Th-1 cytokines.
This well characterized model for murine asthma could be totally blocked using immunization with a Th-1 inducing agent.
There is emerging a tantalizing story that may partially account for the increase in asthma in industrialized nations. If the immune system of children are not busy with multitudes of indigenous infections, the genetics for inducing a Th-2 response to allergens (eg, mites, pets, food) is less encumbered. These results also point to intriguing strategies for immunization to enhance Th-1 responses, and hopefully slowing down or turning off Th-2 responses.