The host adaptive immune response to the Lyme disease pathogen, Borrelia burgdorferi, appears to be ineffective at eradicating infection. One hypothesis to explain the ineffective defense is that an inappropriate helper T cell response to the microorganism is established during infection, and interferes with the appropriate defenses. This idea has received support in other infectious disease models, and has led to the identification of two phenotypes of helper T cell responses, Th1 and Th2. Th1-type responses are associated with delayed type hypersensitivity while Th2 type responses are associated with B cell help. In certain models the presence of Th2 type cells will interfere with the DTH response required to control growth of the infecting agent. Two highly immunogenic outer surface proteins of B. burgdorferi will be tested for their ability to stimulate Th1 and Th2 type of T cell responses, and T cell lines will be established. The T cell response in C3H mice, which readily develop severe arthritis when infected with B. burgdorferi, will be determined at four phases of infection. This will allow tracking of the type of T cell response through early infection, disease evolution, disease regression, and long-term persistence. T cell lines derived at these times will be transferred to infected mice which are immunocompetent, or to mice which are lacking classical T or B cell responses. The effect of Th1 and Th2 type T cells on the progression of disease will be determined. The ability of T cells of a particular type to clear infection, or to exacerbate disease, will be assessed. The requirement for B cells for exertion of the effect of T cells will also be determined. Thus, these studies will provide information on all aspects of the role of the T cell in murine Lyme disease.
