Thomson J A, Troutt A B, Kelso A
Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Immunology. 1993 Feb;78(2):185-92.
The synthesis and role of several lymphokines were examined during contact sensitization to oxazolone (OX). Application of OX to the skin of mice increased the delayed-type hypersensitivity (DTH) response to challenge, serum titres of OX-specific IgG1 and IgG2a, and draining lymph node cell (LNC) numbers. At day 3, LN contained detectable interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-2 or IL-3 mRNAs; IL-3 and higher levels of IL-4, IFN-gamma and GM-CSF mRNAs were measured after 24 hr culture with anti-CD3 antibody in OX-primed but not unprimed LNC. As a result of sensitization, LNC secreted IL-3 constitutively and produced elevated levels of IL-2, IL-3, IL-4 and IFN-gamma in response to anti-CD3 antibody; a similar but weaker lymphokine response was recalled by OX-protein conjugate. CD4+ cells were the major source of the anti-CD3-induced lymphokines except IFN-gamma, which was derived mainly from CD8+ cells. Since both IL-4 and IFN-gamma were synthesized by OX-primed LNC in vivo and in vitro, their role was investigated by administering anti-lymphokine antibodies at the time of sensitization. Anti-IL-4 treatment reduced OX-specific serum IgG1 titres without affecting IgG2a titres, whereas anti-IFN-gamma treatment reduced IgG2a but not IgG1 titres. Although neither antibody altered DTH responsiveness, anti-IFN-gamma treatment markedly increased IL-4 production by CD4+ LNC and reduced IFN-gamma production in vitro, particularly by CD4+ cells. We conclude that endogenous IL-4 and IFN-gamma reciprocally influence the isotype of the Ig response to OX and that IFN-gamma also affects the relative levels of IL-4 and IFN-gamma synthesis by CD4+ LNC.
在对恶唑酮（OX）进行接触致敏期间，对几种淋巴因子的合成及其作用进行了研究。将OX应用于小鼠皮肤可增强对激发的迟发型超敏反应（DTH）、OX特异性IgG1和IgG2a的血清滴度以及引流淋巴结细胞（LNC）数量。在第3天，淋巴结中含有可检测到的白细胞介素-4（IL-4）、干扰素-γ（IFN-γ）和粒细胞-巨噬细胞集落刺激因子（GM-CSF），但未检测到IL-2或IL-3 mRNA；在用抗CD3抗体对经OX致敏而非未致敏的LNC进行24小时培养后，检测到IL-3以及更高水平的IL-4、IFN-γ和GM-CSF mRNA。致敏后，LNC组成性分泌IL-3，并在抗CD3抗体刺激下产生升高水平的IL-2、IL-3、IL-4和IFN-γ；OX-蛋白偶联物可引发类似但较弱的淋巴因子反应。CD4+细胞是抗CD3诱导的淋巴因子的主要来源，但IFN-γ主要来自CD8+细胞。由于IL-4和IFN-γ均可在体内和体外由经OX致敏的LNC合成，因此在致敏时给予抗淋巴因子抗体来研究它们的作用。抗IL-4治疗降低了OX特异性血清IgG1滴度，而不影响IgG2a滴度，而抗IFN-γ治疗降低了IgG2a滴度，但不影响IgG1滴度。虽然两种抗体均未改变DTH反应性，但抗IFN-γ治疗显著增加了CD4+ LNC的IL-4产生，并在体外降低了IFN-γ产生，尤其是CD4+细胞的IFN-γ产生。我们得出结论，内源性IL-4和IFN-γ相互影响对OX的Ig反应的同种型，并且IFN-γ还影响CD4+ LNC合成IL-4和IFN-γ的相对水平。
