The outer surface lipoprotein OspA of Borrelia burgdorferi provides co-stimulatory signals to normal human peripheral CD4+ and CD8+ T lymphocytes.
Studies in man and mice have indicated that T cells induced during Borrelia burgdorferi infection are involved in the pathogenesis of the disease. We analyzed the ability of B. burgdorferi to provide co-stimulatory signals to highly enriched normal human CD2+ T lymphocytes in the presence of suboptimal concentrations of immobilized anti-CD3 antibodies. Here we show that the lipid-containing recombinant outer surface lipoprotein A (rlip-OspA) of B. burgdorferi but not its delipidated derivative rNS1-OspA augmented CD3-induced T cell proliferation in a dose-dependent manner and at levels similar to that obtained with anti-CD28 antibodies. Lipopolysaccharide had no effect in this system at any concentration tested, suggesting that the active principle of co-stimulation is associated with the lipid moiety of rlip-OspA and distinct from conventional lipid A. Furthermore, incubation of CD2+ T cells or selected CD4+ as well as CD8+ subpopulations with rlip-OspA, but not with rNS1-OspA led to the production of interferon (IFN)-gamma, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, but not IL-4. In contrast, co-stimulation of the respective T cell populations with anti-CD28 antibodies resulted in the generation of IFN-gamma, IL-4 and TNF-alpha, but not IL-6. This indicated that the signal transduction pathway induced by rlip-OspA is distinct from that elicited via the CD28 receptor. Co-stimulation of T cells with rlip-OspA also resulted in the development of cytolytic effector cells. In light of the fact that inflamed tissues of B. burgdorferi-infected hosts contain blood leukocytes together with spirochetes, their degradation products, or both, these results suggest that infiltrating CD4+ and CD8+ T cells of any specificities, including spirochetes, autoantigens, or both, participate in the pathogenesis of Lyme disease.
Institute for Immunology, University of Heidelberg, Germany.
H
H
Knigge
M M
MM
Simon
S C
SC
Meuer
M D
MD
Kramer
R
R
Wallich
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D018801:CD2 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D008074:Lipoproteins; D008213:Lymphocyte Activation; D011994:Recombinant Proteins
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018801:CD2 Antigens; D016207:Cytokines; D008074:Lipoproteins; C072045:OspA protein; D011994:Recombinant Proteins