Lymphoid apoptosis in acute canine distemper

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The relationship between the canine distemper virus (CDV) infection and apoptosis in the canine lymphoid tissues was investigated using immunostaining for single stranded DNA (ssDNA), TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method, and electron microscopy. Twenty-six lymphoid tissues from 8 spontaneously CDV-infected dogs and 1 non-infected dog were used, and lesions were classified into 4 groups according to frequency of the CDV-antigen. Histologically, the degree of lymphoid depletion tended to depend on amount of CDV antigen. The numbers of ssDNA- and TUNEL-labeling cells were significantly high in the lymphoid tissues with abundant viral antigen. However, ssDNA- and TUNEL-positive lymphocytes were also frequently found even in the lymphoid tissues where there was only a small amount of CDV-antigen in sinus histiocytes. The incidence and distribution of apoptotic cells in the CDV-antigens-negative lymphoid tissues from infected dogs were equal to those from a non-infected dog. Double labeling immunostaining using a ssDNA and a CDV nucleocapsid protein (CDV-NP) antibody revealed that there were ssDNA positive but CDV-NP negative cells besides those stained doubly positive. Ultrastructurally, lymphocytes in the CDV-infected lymphoid tissues frequently had characteristic morphological features of apoptosis such as apoptotic bodies. All these results suggest that CDV leads to lymphocytic apoptosis directly or indirectly, resulting in severe lymphoid depletion and immunosuppression in acute or subacute phase of CDV infection.犬リンパ組織におけるイヌジステンパーウイルス(CDV)感染とアポトーシスの関係について,一本鎖DNA(ssDNA)とTdT-mediated dUTP-biotin nick end-labeling (TUNEL)法,および電子顕微鏡を用いて検討した.本研究では,8頭のCDV自然感染犬と1頭の非感染犬から採取した26個のリンパ組織を使用し,CDV抗原分布の程度により,各組織を4群に分類した.組織学的に,リンパ濾胞萎縮の程度は,CDV抗原分布と相関していた.ssDNAおよびTUNEL陽性細胞数は,CDV抗原分布が高いリンパ組織で有意に増加していた.また,髄洞の組織球にCDV抗原を少量しか認めないリンパ組織にも,多くのssDNAおよびTUNEL陽性細胞が認められた.CDV感染大のCDV抗原が検出されないリンパ組織におけるアポトーシスの頻度は,非感染犬のリンパ組織と同程度で統計学的な有意差はなかった.ssDNAとCDV-NPの二重免疫染色では,ssDNA/CDV-NP陽性細胞と同時に,CDV陰性でssDNAにのみ陽性を示す細胞も認められた.起微細形態的にCDV感染リンパ組織において,アポトーシス小体などアポトーシスに特徴的形態が認められた.以上のことから,CDVはリンパ球に直接的または間接的にアポトーシスを誘起し,その結果,急性または亜急性感染期に重度のリンパ球減少症と免疫抑制を感染犬に引き起こしていると推察された.
Japanese Society of Veterinary Science,日本獣医学会の論文
2004-02-25

Lymphoid apoptosis in acute canine distemper

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