Disagreement surrounds the importance of the T-cell response to B. burgdorferi and the overall importance of the cellular immune response relative to the humoral immune response.  The cellular immune response to B. burgdorferi has been studied more extensively in the murine model than in humans.  CD4 T cells are thought to control the response, because giving mice anti-CD4 mAb increases the bacteria’s infectivity as well as the severity of Lyme arthritis (Pohl-Koppe et. al. 1998).  Keane-Myers and Nickell further examined the role of CD4+ and CD8+ helper T cells in fighting B. burgdorferi infection.  They found that the depletion of CD4+ T cells led to more severe disease and increased susceptibility, while depletion of CD8+ T cells led to increased protection and milder disease.  CD8+ T cells are thought to exacerbate B. burgdorferi infection by interfering with the protective immune response, which is called negative immunoregulation (Kean-Myers and Nickell, 1995, “T Cell Subset-Dependent Modulation of Immunity to Borrelia burgdorferi in Mice”).

While a great deal is not known about the T-cell response in Lyme disease, the Th1 response is thought to dominate the cellular immune response. Experimental support for the dominance of the Th1 response over the Th2 response is shown by the examination of cytokines in the synovial fluid of patients with Lyme arthritis:  Th1 cytokines are more abundant that those of Th2 (Diterich and Hartung, 2001). Production of IL-12 is induced in macrophages and dendritic cells that engulf pathogens, and IL-12 subsequently causes the production of IFN-γ and a Th1-dominanated response (Anguita et. al., 1996). Filugueira et. al. showed that dendritic cells secrete IL-12 after phagocytosing B. burgdorferi spirochetes, which would explain the Th1-dominated response (1996).  In one experiment, Lyme disease-infected mice were given anti-IL-12 antibody, which reduced the strength of the Th1 response overall (Diterich and Hartung, 2001). In another experiment, mice with Th1 cells were found to be more susceptible to arthritis, while mice with a greater Th2 response showed greater resistance to developing severe arthritis (McKisic et. al., 2000).  This demonstrates one of the key mechanisms by which B. burgdorgeri effectively causes disease; mice with an atypical Th2-dominated response to B. burgdorferi were more likely to have milder infection.  The host’s normal Th1-dominated response to the bacterium leads to more severe disease. Thus, the bacterium induces the weaker cell-mediated immune response, aiding the bacterium’s overall pathogenic ability.  

Keane-Meyers and Nickell found that C3H/HeN mice were susceptible to B. burgdorferi infection due to their Th1-dominated immune response with IFN-γ production, while the BALB/c mouse was protected from B. burgdorferi infection due to its Th2-dominant immune response with mostly IL-4 production (Keane-Meyers and Nickell, 1995, “Role of IL-4 and IFN-γ in Modulation of Immunity to Borrelia burgdorferi in Mice”). This claim was supported by the fact that when BALB/c mice were treated with neutralizing anti-IL-4 mAb, the infection by B. burgdorferi led to increasingly swollen joints and a greater number of bacteria overall.  On the other hand, when C3H/HeN mice were treated with anti-IFN-γ mAb, both swelling and spirochete count at death was reduced (Kean-Meyers and Nickell, 1995, “Role of IL-4 and IFN-γ in Modulation of Immunity to Borrelia burgdorferi in Mice”).

During attacks of Lyme arthritis, the B. burgdorferi-specific Th1 response is demonstrated through the dominating presence of Th1 cytokines in the synovial fluid; Th2 cytokines are also present but to a lesser degree (Steere, 2001).  Yssel et. al. found that T-cells extracted from the peripheral blood and synovial fluid of patients with Lyme arthritis were mostly Th1 cells that responded to a diverse set of spirochetal antigens. When activated, these T-cells produced mostly IL-2 and IFN-γ with little IL-4 and IL-5, which parallels the normal secretions of Th1 cells.  This response proves to be problematic for the host and aids in B. burgdorferi’s ability to evade the host immune system.  Extracellular pathogens like B. burgdorferi are most successfully fought with Th2 cells, while intracellular pathogens are most effectively fought with Th1 cells. The selective response by Th1 cells and the subsequent influx of Th1 cytokines aids in the inflammatory response seen in Lyme arthritis (Yssel et. al., 1991).  IFN-γ induces the release of various inflammatory mediators:  IL-1, TNF-α, and IL-6 (Keane-Meyers and Nickell, 1995, “Role of IL-4 and IFN-γ in Modulation of Immunity to Borrelia burgdorferi in Mice”). TNF-α may induce the resorption of bone and cartilage, contributing to the pathophysiology of Lyme arthritis (Yssel et. al., 1995). Overall, the Th1-dominated cellular response to B. burgdorferi contributes pathophysiologically to inflammation and joint damage in Lyme arthritis (Yssel et. al, 1991).

Pohl-Koppe et. al. studied the cellular immune response in patients with chronic Lyme disease and neuroborreliosis and found that a particular set of T-cells was produced that secreted both IFN-γ and IL-10, and IL-12 secreted by PBMC was needed for the development of this T-cell subset.   Anti-IL-12 antibodies suppressed the secretion of IFN-γ and IL-10 in these T-cells (1998).

This page was created for an undergraduate Immunology course, Biology 307, at Davidson College in the Spring semester of 2007 under Dr. Sophia Sarafova (sasarafova@davidson.edu)

Please direct all comments and questions to Meredith Prasse (meprasse@davidson.edu)