Makino M, Yoshimatsu K, Azuma M, Okada Y, Hitoshi Y, Yagita H, Takatsu K, Komuro K
Department of Bacterial and Blood Products, National Institute of Health Japan, Tokyo.
J Immunol. 1995 Jul 15;155(2):974-81.
Murine AIDS (MAIDS) is induced by infection with the replication-defective virus (BM5def) component in the LP-BM5 murine leukemia virus (MuLV) mixture. The disease is characterized by polyclonally activated CD4+ T cells and B cells. It is known that BM5def is expressed at highest levels in B lymphocytes and that B cells serve as viral antigen-presenting cells. Full and sustained activation of CD4+ T cells against a conventional Ag usually requires both TCR and costimulating signals. Among various molecules known to provide costimulatory function, the expression of CD54 (ICAM-1) and CD11a/CD18 (LFA-1) on MAIDS B cells was increased, whereas that of CD2, heat-stable Ag (CD24), CD80 (B7-1), and CD86 (B7-2) was unchanged from normal. C57BL/6 mice depleted of both CD54 and CD11a expression as a result of chronic administration of mAb had developed no MAIDS at 4 wk and 8 wk after LP-BM5 MuLV infection. In addition, the proliferative response of B cells to mitogen was well conserved, whereas MAIDS-associated increases in serum Ig levels were inhibited. Replication of BM5def was suppressed markedly in infected mice treated with the CD54 and CD11a mAbs. These results suggest that the CD54/CD11a signal transduction pathway is a critical determinant of MAIDS development, and the lack of an immune response against viral Ag is enough to suppress BM5def replication and to prevent MAIDS.
小鼠获得性免疫缺陷综合征（MAIDS）是由感染LP - BM5小鼠白血病病毒（MuLV）混合物中的复制缺陷型病毒（BM5def）成分诱导产生的。该疾病的特征是多克隆激活的CD4 + T细胞和B细胞。已知BM5def在B淋巴细胞中表达水平最高，且B细胞可作为病毒抗原呈递细胞。针对传统抗原的CD4 + T细胞的完全且持续激活通常需要TCR和共刺激信号。在已知具有共刺激功能的各种分子中，MAIDS B细胞上CD54（细胞间黏附分子-1）和CD11a/CD18（淋巴细胞功能相关抗原-1）的表达增加，而CD2、热稳定抗原（CD24）、CD80（B7 - 1）和CD86（B7 - 2）的表达与正常情况相比没有变化。由于长期施用单克隆抗体而使CD54和CD11a表达均缺失的C57BL/6小鼠在感染LP - BM5 MuLV后4周和8周未发生MAIDS。此外，B细胞对有丝分裂原的增殖反应得到很好的保留，而与MAIDS相关的血清Ig水平升高受到抑制。在用CD54和CD11a单克隆抗体处理的感染小鼠中，BM5def的复制受到明显抑制。这些结果表明，CD54/CD11a信号转导途径是MAIDS发展的关键决定因素，并且缺乏针对病毒抗原的免疫反应足以抑制BM5def复制并预防MAIDS。
