The outer surface lipoprotein OspA of Borrelia burgdorferi provides co‐stimulatory signals to normal human peripheral CD4+ and CD8+ T lymphocytes

Abstract

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)‐γ, interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α, but not IL‐4. In contrast, co‐stimulation of the respective T cell populations with anti‐CD28 antibodies resulted in the generation of IFN‐γ, IL‐4 and TNF‐α, 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.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady

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