CD4+ T helper 1 cells facilitate regression of murine Lyme carditis.
Murine Lyme borreliosis, caused by infection with the spirochete Borrelia burgdorferi, results in acute arthritis and carditis that regress as a result of B. burgdorferi-specific immune responses. B. burgdorferi-specific antibodies can attenuate arthritis in mice deficient in both B cells and T cells but have no effect on carditis. Because macrophages comprise the principal immune cell in carditis, T-cell responses that augment cell-mediated immunity may be important for carditis regression. To investigate this hypothesis, we examined the course of Lyme carditis in mice selectively deficient in B cells or alphabeta T cells. Our results show that carditis regresses in B-cell-deficient B10.A(k) mice but not in alphabeta T-cell-deficient mice, independently of the mouse strain background. Despite prominent macrophage infiltrates, hearts from B. burgdorferi-infected alphabeta T-cell-deficient mice had less mRNA for tumor necrosis factor alpha as measured by reverse transcription-PCR compared to infected control mice. Anti-inflammatory cytokine mRNA levels were equivalent. Adoptive transfer of gamma interferon-secreting CD4+ T cells into infected alphabeta T-cell-deficient mice promoted carditis resolution. These results show that alphabeta T cells can promote resolution of murine Lyme carditis and are the first demonstration of a beneficial role for CD4+ T helper 1 cells in this disease.
Bockenstedt
L K
LK
Department of Internal Medicine, Yale University School of Medicine, Yale University, New Haven, Connecticut 06520-8031, USA. linda.bockenstedt@yale.edu
Kang
I
I
Chang
C
C
Persing
D
D
Hayday
A
A
Barthold
S W
SW
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015748:Borrelia burgdorferi Group; D007371:Interferon-gamma / Q000096:biosynthesis; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D016513:Mice, SCID; D009205:Myocarditis / Q000276:immunology* / Q000382:microbiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma