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 αβ T cells. Our results show that carditis regresses in B-cell-deficient B10.A(k) mice but not in αβ T-cell-deficient mice, independently of the mouse strain background. Despite prominent macrophage infiltrates, hearts from B. burgdorferi-infected αβ 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 αβ T-cell-deficient mice promoted carditis resolution. These results show that αβ 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.

由伯氏疏螺旋体（Borrelia burgdorferi）感染引发的鼠类莱姆疏螺旋体病，可引发急性关节炎与心肌炎，此类病症可通过针对伯氏疏螺旋体的特异性免疫应答实现消退。针对伯氏疏螺旋体的特异性抗体可在B细胞与T细胞联合缺陷的小鼠中缓解关节炎症状，但对心肌炎无改善作用。由于巨噬细胞是心肌炎中的主要免疫细胞，能够增强细胞免疫的T细胞应答或许对心肌炎消退至关重要。为验证这一假说，我们检测了选择性缺失B细胞或αβ T细胞的小鼠的莱姆心肌炎病程。研究结果显示，心肌炎在B细胞缺陷型B10.A(k)小鼠中可自行消退，但在αβ T细胞缺陷型小鼠中无法消退，且该现象与小鼠品系背景无关。尽管受伯氏疏螺旋体感染的αβ T细胞缺陷型小鼠心脏存在显著的巨噬细胞浸润，但其肿瘤坏死因子α（tumor necrosis factor alpha, TNF-α）的mRNA水平经逆转录聚合酶链式反应（reverse transcription-PCR, RT-PCR）检测后，较感染对照组小鼠更低。抗炎细胞因子的mRNA水平则无显著差异。向受感染的αβ T细胞缺陷型小鼠过继转移分泌γ干扰素（gamma interferon）的CD4(+) T细胞，可促进心肌炎的消退。上述结果表明，αβ T细胞可促进鼠类莱姆心肌炎的消退，这也是首次证实CD4(+) T辅助1细胞在该疾病中发挥有益作用。