Allergic asthma is a chronic inflammatory disease and despite the introduction of potent and effective drugs, the prevalence has increased substantially over the past few decades. The explanation that has attracted the most attention is the 'hygiene hypothesis', which suggests that the increase in allergic diseases is caused by a cleaner environment and fewer childhood infections. Indeed, certain mycobacterial strains can cause a shift from T-helper cell 2 (Th2) to Th1 immune responses, which may subsequently prevent the development of allergy in mice. Although the reconstitution of the balance between Th1 and Th2 is an attractive theory, it is unlikely to explain the whole story, as autoimmune diseases characterized by Th1 responses can also benefit from treatment with mycobacteria and their prevalence has also increased in parallel to allergies. Here we show that treatment of mice with SRP299, a killed Mycobacterium vaccae-suspension, gives rise to allergen-specific CD4+CD45RB(Lo) regulatory T cells, which confer protection against airway inflammation. This specific inhibition was mediated through interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), as antibodies against IL-10 and TGF-beta completely reversed the inhibitory effect of CD4+CD45RB(Lo) T cells. Thus, regulatory T cells generated by mycobacteria treatment may have an essential role in restoring the balance of the immune system to prevent and treat allergic diseases.

SummaryBorrelia burgdo~feri, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdo~feri outer surface protein (Osp) A protects mice from spirochete infection. Here we report on the expression of OspA on spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdotferi infection. When OspA antibody was administered to mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing spirochetes in the tick gut and block transmission from the vector to the host.T he spirochetal agent of Lyme disease, Borrelia burgdooCeri is transmitted by Ixodes ticks. In unfed nymphal ticks, spirochetes are found in the gut (l). During tick feeding, the bacteria disseminate to the salivary glands and infect the vertebrate host (2-4). A vaccine based on B. burgdo~ri outer surface protein (Osp) A which protects mice from infection is currently being tested in human trials (5-7). Here we examine the expression of OspA on spirochetes within engorging nymphs and relate OspA expression to protection afforded by OspA antibody. Materials and MethodsMice. Pathogen-free C3H/HeN (C3H) mice were purchased from the National Institutes of Health (Bethesda, MD). Maintenance and Infection of Ticks. Ixodes dammini (also known as L scapularis)were derived from a colony in its second generation from field-collected adults, and were free of inherited infection. Larvae were allowed to engorge on CD-1 mice that had been infected 2 wk previously by the bites of three to five nymphal I. dammini containing the N40 strain of B. burgdotferi.Engorged larvae were collected, held in mesh-covered plaster of paris containing vials, and were allowed to molt at 95% relative humidity at 21~ The infected nymphs were held under the same conditions before their use in experiments, usually within 2 mo of molting. Antibody Staining of OspA-expressing Spirochetes in NymphalTicks. Guts and salivary glands were dissected out of nymphs and prepared for antibody staining as previously described (2). mAb CIII.78, which binds to a COOH-t...

Modern vaccinations, fear of germs and obsession with hygiene are depriving the immune system of the information input upon which it is dependent. This fails to maintain the correct cytokine balance and fine-tune T-cell regulation, and may lead to increased incidences of allergies and autoimmune diseases. If humans continue to deprive their immune systems of the input to which evolution has adapted it, it may be necessary to devise ways of replacing it artificially.

As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy. Such interrogation of the tumor, blood, and host immune parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. To approach these opportunities for progress, the Society for Immunotherapy of Cancer (SITC) reconvened the Immune Biomarkers Task Force. Comprised of an international multidisciplinary panel of experts, Working Group 4 sought to make recommendations that focus on the complexity of the tumor microenvironment, with its diversity of immune genes, proteins, cells, and pathways naturally present at baseline and in circulation, and novel tools to aid in such broad analyses.

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