VESICULAR STOMATITIS-VIRUS INDIANA GLYCOPROTEIN AS A T-CELL-DEPENDENT AND T-CELL-INDEPENDENT ANTIGEN

VESICULAR STOMATITIS-VIRUS INDIANA GLYCOPROTEIN AS A T-CELL-DEPENDENT AND T-CELL-INDEPENDENT ANTIGEN
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DOI:
10.1128/jvi.68.6.3650-3655.1994
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发表时间:
1994-06-01
影响因子:
5.4
通讯作者:
ZINKERNAGEL, RM
ZINKERNAGEL, RM
中科院分区:
医学2区
文献类型:
--
作者:
FREER, G;BURKHART, C;ZINKERNAGEL, RM

文献摘要

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在几种t细胞缺陷小鼠模型中,对水疱性口炎病毒(VSV)的中和性免疫球蛋白M (IgM)反应已被证明在很大程度上与t细胞无关。通过使用不同抗原形式的VSV, VSV抗原剂量可以在体内分级(感染性远远大于紫外线灭活>福尔马林灭活)。目前的研究揭示了在裸鼠静脉注射低剂量非传染性uv灭活VSV血清型印第安纳(VSV- ind)时,仅当小鼠输注VSV- ind特异性辅助性T细胞时,T细胞依赖性成分中和IgM反应。相反,用传染性VSV免疫的裸鼠在体内产生更大的抗原剂量,能够在没有T细胞的情况下产生IgM反应。这些结果表明,IgM对低剂量VSV-IND糖蛋白(G)的反应依赖于t细胞。用传染性VSV免疫的裸鼠也产生可变但低VSV- ind中和的IgG反应。VSV-IND基质(M)特异性辅助t细胞系使这种反应更加一致,更高,更持久。因此(i) VSV- g诱导了一种大部分不依赖t细胞但部分依赖t细胞的IgM(后者在低剂量抗原下效果最好)和(ii)裸鼠对VSV的抗体反应通过剂量依赖的步骤进行,即IgM和IgG。结果表明辅助性T细胞的主要作用可能是扩大和维持B细胞分化的单个步骤。
The neutralizing immunoglobulin M (IgM) response to vesicular stomatitis virus (VSV) has been shown to be largely T-cell independent in several T-cell-deficient models of mice. By using different antigen forms of VSV, VSV antigen doses could be graded in vivo (infectious much greater than UV inactivated > formalin inactivated). The present study reveals a T-cell-dependent component of the neutralizing IgM response in nude mice given intravenous injections of low doses of noninfectious UV-inactivated VSV serotype Indiana (VSV-IND) only if the mice are transfused with VSV-IND-specific helper T cells. Instead, nude mice immunized with infectious VSV, which leads to greater antigen doses in vivo, were able to mount an IgM response in the absence of T cells. These results indicate that the IgM response to low doses of VSV-IND glycoprotein (G) is T-cell dependent. Nude mice immunized with infectious VSV also made a variable but low VSV-IND-neutralizing IgG response. A VSV-IND matrix (M)-specific helper T-cell line rendered this response more consistent, much higher, and longer lasting. Thus (i) VSV-G induces a mostly T-cell-independent but partially T-cell-dependent IgM (the latter can be visualized best at low doses of antigen) and (ii) the antibody response to VSV in nude mice proceeds through steps, i.e., IgM and IgG, that are dose dependent. The results suggest that the predominant role of helper T cells may be to expand and maintain the individual steps of differentiating B cells.