IDENTIFICATION OF A T-CELL SUBSET CAPABLE OF BOTH IFN-GAMMA AND IL-10SECRETION IN PATIENTS WITH CHRONIC BORRELIA-BURGDORFERI INFECTION

A novel population of both IFN-gamma- and IL-10-secreting human T cell s that differentiate in the presence of exogenous IL-12 in vitro has r ecently been described. Whether this T cell population exists in vivo is unknown, Borrelia burgdorferi, the etiologic agent of Lyme disease, can induce a chronic infection in the presence of a rigorous humoral immune response. We established T cell lines specific for B. burgdorfe ri and tetanus toxoid from subjects with chronic B. burgdorferi infect ion and healthy controls in limiting dilution experiments and assessed proliferation and cytokine secretion. As expected, higher frequencies of B. burgdorferi-specific precursor T cells were observed in Lyme pa tients compared with controls. In both groups of subjects, T cell line s specific for B. burgdorferi secreted high amounts of IFN-gamma. Howe ver, in patients with Lyme disease, 27% of T cell lines secreted not o nly IFN-gamma but also IL-10, which was only observed in 0.6% of B. bu rgdorferi-reactive T cell lines generated from controls and in none of the tetanus toxoid-reactive T cell lines generated from either Lyme p atients and controls. Single cell PHA cloning confirmed that both cyto kines were secreted from one clonally expanded precursor cell, Whole m ononuclear cells from B. burgdorferi-infected individuals, but not fro m controls, secreted IL-12. Moreover, neutralizing anti-IL-12 mAbs inh ibited the generation of the IFN-gamma/IL-10 population, These data de monstrate that this novel population of IL-12-induced IFN-gamma/IL-10- secreting T cells is generated in response to chronic B. burgdorferi i nfection.