Long-term study of cell-mediated responses to Borrelia burgdorferi in the laboratory mouse

Abstract

Borrelia burgdorferi infection of disease-susceptible (C3H) and -resistant (BALB) mice resulted in impaired proliferation to both T- and B-cell mitogens up to 30 days after inoculation. Interleukin-2 and -4 production was also impaired, paralleling the T-cell response to concanavalin A. Impaired lymphocyte proliferation could not be attributed to diminished numbers of T or B cells and was found to depend on the lymphoid organ (spleen or lymph node) examined. Prostaglandin production accounted for part of this immune dysfunction. Attempts to assess antigen-specific proliferation to B. burgdorferi were inconsistent, and delayed-type hypersensitivity responses were not detected. Adoptive transfer of T-enriched cells from chronically infected donors failed to prevent infection and disease development in recipient C3H mice. The current study emphasizes caution in the study of B. burgdorferi antigen-specific assays and argues against the role of a vigorous T-cell response in Lyme borreliosis in infected laboratory mice.

Significant differences between the Borrelia-infection and Borrelia-vaccination and -infection models of Lyme arthritis in C3H/HeN mice

“…The traditional Borrelia-infection model in C3H mice exhibits pathological changes driven by cells of innate immunity (Barthold, 1996). In addition, this model uses young mice and inocula of Borreliae that may be below the threshold to detect T cell responses consistently (de Souza et al, 1993). This inflammation initially manifests within days after infection and peaks 2-3 weeks later, before subsiding (Barthold, 1996).…”

The cell-mediated immune response to Borrelia afzelii, garinii and burgdorferi in C57BL/6 mice is dependent on antigen specificity

“…It was reported that T-lymphocytes are involved in the development of severe destructive arthritis in hamsters infected with Borrelia [34]. However, DeSouza et al [18] showed a relatively poor antigen-speci¢c T-cell response in experimentally infected mice detected by the lymphocyte proliferation assay. Zeidner et al [35] demonstrated that the immune response in mice could be either of the Th1 or Th2 type, depending on the cytokine pro¢le and relative genetic susceptibility to Lyme disease.…”

“…3). The results obtained in assays using unseparated splenocytes are di¤cult to interpret because the antigen-speci¢c T-cell response in Borrelia infections is relatively poor [18,30,34]. At the same time the simultaneous B-cell growth caused by B-lymphocyte mitogenic factors present in Borrelia antigen preparations, even in a 120-h culture, can lead to misinterpretation of the result.…”

“…There is no major disagreement that antibodies are important in immunity against B. burgdorferi s.l., but the cellular immune response studies in Lyme disease have led to variable and con£icting conclusions [14^17]. Some reports have revealed a vigorous antigen-speci¢c response by the peripheral blood lymphocytes from infected humans, and by the spleen and lymph node cells from infected mice [5,18,19]. On the other hand, some of the experiments performed with unseparated Borrelia antigen preparations give the impression that the stimulation is mitogenic, acting primarily on B cells [20,21].…”

Modulation of lymphocyte proliferative responses by a canine Lyme disease vaccine of recombinant outer surface protein A (OspA)

“…Suppression of in vitro mitogen-or antigen-mediated proliferative responses of lymphocytes and reduced production of interleukin-2 (IL-2) from lymphocytes were demonstrated using protein extracts of B. burgdorferi. These early studies were con¢rmed by a report of de Souza et al [8], who observed that B. burgdorferi infection in mice resulted in impaired T and B cell proliferation to mitogens and reduced IL-2 and IL-4 production. The nature of the B. burgdorferi proteins responsible for suppression of cellular immunity has not been de¢ned.…”