CD4+ T helper 1 cells facilitate regression of murine Lyme carditis
CD4+ T helper 1 cells facilitate regression of murine Lyme carditis
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DOI：
10.1128/iai.69.9.5264-5269.2001
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发表时间：
2001-09-01
影响因子：
3.1
通讯作者：
Barthold, SW
中科院分区：
文献类型：
--
作者：
Bockenstedt, LK;Kang, I;Barthold, SW
小鼠莱姆病是由伯氏疏螺旋体感染引起的，可导致急性关节炎和心脏炎，并可因伯氏疏螺旋体特异性免疫反应而消退。伯氏疏螺旋体特异性抗体可以减轻缺乏B细胞和T细胞的小鼠的关节炎，但对心脏炎没有作用。由于巨噬细胞是心肌炎的主要免疫细胞，增强细胞介导免疫的t细胞反应可能对心肌炎的消退很重要。为了研究这一假设，我们在选择性缺乏B细胞或α β T细胞的小鼠中检查了莱姆病的病程。我们的研究结果表明，b细胞缺陷B10的心脏炎会消退。A(k)小鼠，而不是在α β t细胞缺陷小鼠中，独立于小鼠品系背景。尽管有明显的巨噬细胞浸润，但通过逆转录- pcr检测，与感染对照小鼠相比，伯氏疏螺旋体感染的α β t细胞缺陷小鼠的心脏中肿瘤坏死因子α的mRNA较少。抗炎细胞因子mRNA水平相当。将分泌γ干扰素的CD4(+) T细胞过继转移到感染的α β T细胞缺陷小鼠体内，可促进心肌炎的消退。这些结果表明，α - β T细胞可以促进小鼠莱姆病的消退，并且首次证明了CD4(+) T辅助1细胞在该疾病中的有益作用。
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 alpha beta T cells. Our results show that carditis regresses in B-cell-deficient B10.A(k) mice but not in alpha beta T-cell-deficient mice, independently of the mouse strain background. Despite prominent macrophage infiltrates, hearts from B. burgdorferi-infected alpha beta 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 alpha beta T-cell-deficient mice promoted carditis resolution. These results show that alpha beta 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.