Analysis of T lymphocytes cloned from the synovial fluid and blood of a patient with lyme arthritis

Abstract

Cloned T lymphocytes reactive with Borrelia burgdorferi proteins were isolated from a patient with chronic Lyme arthritis. All of the T cell clones which proliferated in response to Borrelia proteins were CD3 + CD4 + CD8 - TCR alpha beta + and HLA-DR restricted. One T cell clone (GN30) exhibited HLA-DR-restricted cytotoxic activity against antigen-presenting cells pulsed with Borrelia antigen. In response to Borrelia antigen, the T cell clones produced TNF-alpha, INF-gamma, and GM-CSF. There are at least three distinct spirochetal proteins recognized by the four T cell clones analyzed. Purified Borrelia proteins triggered the HLA-DR-restricted proliferative and cytotoxic responses, as well as lymphokine secretion by two of the T cell clones. The spirochetal protein which triggered the HLA-DR-restricted proliferative and cytotoxic activities of the T cell clone (GN30) isolated from synovial fluid is the 41 kd flagellar protein.

Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi OspA or B.

“…Recombinant OspB has a lower molecular mass than native OspB because of the removal of the OspB leader sequence resulting in a lack of lipidation. In addition, the antibody titers to whole cell lysates of B. burgdorferi by ELISA was similar in OspA transgenic mice and nontransgenic littermates (controls) immunized with 10 Mg of heat-killed spirochetes in CFA-in both cases, antibodies to B. burgdorferi were detectable at a serum dilution of 1:100,000.…”

“…Previous studies have implicated the immune responses to OspA and B in the pathogenesis of Lyme arthritis, both in animal models of disease and in patient populations (7,(10)(11)(12)(30)(31)(32). For example, OspA and B selected timepoints between 14 and 180 d. Tissues (blood, spleen and bladder) were cultured in BSK medium for 2 wk and examined by darkfield microscopy for the presence of spirochetes.…”

“…These studies have led to the proposal that the immune response to OspA may be directly involved in the pathogenesis of disease. Moreover, Peltz and his associates identified Thi T cell clones that responded to OspA in Lyme arthritis synovial fluid and postulated that the cellular immune response to OspA contributes to the genesis of disease (10,11). Peltz's group then further demonstrated that cellular reactivity to diverse epitopes of OspA, and expansion of the Vf5 T cell population, is evident in patients with Lyme arthritis (12,13), While these studies suggest that OspA or B specific immune reactivity is associated with the development of arthritis, a cause and effect relationship between an OspA or B response and disease has not been established.…”

Effect of anti-interleukin 12 treatment on murine lyme borreliosis.

“…The finding that the treatment with anti-IL-12 decreases the Th1 responses in vivo and consequently the degree of acute disease, indicates that the development of this type of T cell response is responsible for some of the arthritis that results from spirochetal infection. Th1 responses are produced during human Lyme disease (9,10), suggesting a correlation between the development of Th1 responses against B. burgdorferi and the severity of human Lyme disease. Our results would indicate that immune responses that can be blocked by anti-IL-12 contribute to the pathogenesis of acute murine Lyme arthritis.…”

“…The pathogenesis of Lyme arthritis is multifactorial and may be related to the host's major histocompatibility haplotype, humoral and cellular immune responses directed towards B. burgdorferi , and/or spirochetal virulence (5)(6)(7). Several studies have correlated the presence of human CD4 ϩ T cell helper (Th1) 1 type responses with the pathogenesis of persistent arthritis (8)(9)(10).…”