T cell subset-dependent modulation of immunity to Borrelia burgdorferi in mice.
The possible involvement of specific T cells in resolution of infections with Borrelia burgdorferi (Bb), the causative agent of human Lyme disease, has not been adequately studied. To investigate the potential role of T cell subsets in resistance, we have depleted mice of CD4+ and CD8+ T cell subsets in vivo by the administration of specific mAbs and have examined outcomes after infection with Bb. Our results indicate that CD4+ T cells are required for immunologic control of spirochete levels, because their depletion in both susceptible C3H/HeN and resistant BALB/c mice increased the severity of arthritis and the numbers of spirochetes found in joints and skin, as compared with Bb-infected mice treated with a control mAb. In contrast, the CD8+ T cell compartment, particularly in susceptible C3H/HeN mice, appears to promote the disease process, possibly by interfering with the generation of protective immunity, as abrogation of this subset in vivo led to a reduction in both arthritis and in spirochete levels found in joints and skin when compared with Bb-infected control mice. Our inability to establish a correlation between resistance and Bb-specific IgG Ab levels in these mice raises the possibility that Ab-independent mechanisms are important in protection. These findings suggest that the final outcome in Bb-infected hosts may be the net effect of antagonistic influences exerted by CD4+ and CD8+ T cell subsets.
Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205.
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Keane-Myers
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Nickell
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015748:Borrelia burgdorferi Group / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G