Herzog W R, Meade R, Pettinicchi A, Ptak W, Askenase P W
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
J Immunol. 1989 Mar 15;142(6):1803-12.
The elicitation of delayed-type hypersensitivity (DTH) reactions in mice is caused by the sequential action of two different T cells. An early-acting, DTH-initiating T cell produces an Ag-specific T cell factor, that is analogous to IgE antibody and initiates DTH by sensitizing the local tissues for release of the vasoactive amine serotonin. In picryl chloride or oxazolone contact sensitivity, this T cell factor is Ag-specific, but MHC unrestricted. We, therefore, hypothesized that DTH-initiating T cells are primitive T cells with Ag receptors that can bind Ag without MHC restriction. In order to characterize the origin of this DTH-initiating T cell and the conditions that are necessary for its development, we contact-sensitized various strains of immunodeficient mice. Surprisingly, we found that the early phase of DTH was present in athymic nude mice. In contrast, the early component of DTH was absent in mice with severe combined immunodeficiency. These mice lack T and B cells, but have NK cells. These findings suggested that the early component of DTH was not caused by NK cells, and was caused by cells belonging to a lineage from a rearranging gene family. The early component of DTH in nude mice was Ag specific, was caused by MHC unrestricted Thy-1+ T cells, and was mediated by Ag-binding, Ag-specific T cell factors. We found that DTH-initiating, T cell-derived, Ag-binding molecules from nude mice and normal CBA/J mice had the same functional properties. The early component of DTH was elicited in two different systems (contact sensitivity and SRBC-specific DTH) in two strains of nude mice (BALB/c athymic nudes and CByB6F1/J-nu) from two different suppliers, but not in BALB/c and athymic nudes from a third supplier. From these findings we concluded that DTH-initiating T cells, which produce IgE-like Ag-specific T cell factors, are present in some strains of athymic nude mice and thus are relatively thymic independent T cells.
小鼠迟发型超敏反应（DTH）的引发是由两种不同T细胞的相继作用所致。一种早期作用、引发DTH的T细胞产生一种抗原特异性T细胞因子，该因子类似于IgE抗体，通过使局部组织致敏以释放血管活性胺5-羟色胺来引发DTH。在苦味酸氯或恶唑酮接触性敏感反应中，这种T细胞因子是抗原特异性的，但不受MHC限制。因此，我们推测引发DTH的T细胞是具有能在无MHC限制情况下结合抗原的抗原受体的原始T细胞。为了表征这种引发DTH的T细胞的起源及其发育所需的条件，我们对各种免疫缺陷小鼠品系进行了接触致敏。令人惊讶的是，我们发现无胸腺裸鼠中存在DTH的早期阶段。相反，严重联合免疫缺陷小鼠中DTH的早期成分缺失。这些小鼠缺乏T细胞和B细胞，但有NK细胞。这些发现表明DTH的早期成分不是由NK细胞引起的，而是由属于重排基因家族谱系的细胞引起的。裸鼠中DTH的早期成分是抗原特异性的，由不受MHC限制的Thy-1 + T细胞引起，并由抗原结合、抗原特异性T细胞因子介导。我们发现来自裸鼠和正常CBA/J小鼠的引发DTH的、T细胞衍生的、抗原结合分子具有相同的功能特性。DTH的早期成分在来自两个不同供应商的两株裸鼠（BALB/c无胸腺裸鼠和CByB6F1/J-nu）的两种不同系统（接触性敏感反应和SRBC特异性DTH）中引发，但在来自第三个供应商的BALB/c和无胸腺裸鼠中未引发。从这些发现中我们得出结论，产生IgE样抗原特异性T细胞因子的引发DTH的T细胞存在于某些无胸腺裸鼠品系中，因此是相对不依赖胸腺的T细胞。
