Kavanagh E G, Kelly J L, Lyons A, Soberg C C, Mannick J A, Lederer J A
Department of Surgery (Immunology), Harvard Medical School/Brigham and Women's Hospital, Boston, Mass 02115, USA.
Surgery. 1998 Aug;124(2):269-76; discussion 276-7.
The mechanisms responsible for altered T-cell responses and cytokine production after injury are not well understood. We used T-cell receptor (TCR) transgenic mice to study burn injury effects on naive versus antigen-activated CD4+ T cells in vivo.
One week after sham or burn injury, lymph node cells were prepared from TCR transgenic mice and stimulated with TCR transgene-specific antigens. T-cell proliferation was measured and culture supernatants were tested for interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, and IL-10 by enzyme-linked immunosorbent assay (ELISA). Burn injury effects on antigen-activated T cells were studied by immunizing TCR transgenic or wild-type mice at the time of injury.
The antigen-stimulated proliferation of native CD4+ T cells was unaffected by burn injury and no increase in T-helper 2 (Th2)-type cytokine production was observed. Instead, burn injury augmented INF-gamma production by naive CD4+ transgenic T cells, and IL-2 production was marginally reduced. Thus, burn injury primed native T cells for an enhanced Th1-type response. In contrast, antigen-specific proliferation, IL-2, and IFN-gamma production by T cells harvested from immunized wild-type mice were suppressed. Unexpectedly, high mortality was observed when burn-injured TCR transgenic mice were immunized.
Our results show that burn injury has differential effects on naive and antigen-activated CD4+ T cells and can prime naive CD4+ T cells.
损伤后T细胞反应和细胞因子产生改变的机制尚未完全明确。我们使用T细胞受体（TCR）转基因小鼠来研究烧伤对体内初始与抗原激活的CD4+ T细胞的影响。
在假手术或烧伤损伤后一周，从TCR转基因小鼠制备淋巴结细胞，并用TCR转基因特异性抗原进行刺激。通过酶联免疫吸附测定（ELISA）测量T细胞增殖，并检测培养上清液中的白细胞介素-2（IL-2）、干扰素-γ（IFN-γ）、IL-4和IL-10。通过在损伤时免疫TCR转基因或野生型小鼠来研究烧伤对抗原激活的T细胞的影响。
初始CD4+ T细胞的抗原刺激增殖不受烧伤损伤的影响，未观察到辅助性T细胞2（Th2）型细胞因子产生增加。相反，烧伤损伤增强了初始CD4+转基因T细胞的INF-γ产生，IL-2产生略有减少。因此，烧伤损伤使初始T细胞引发增强的Th1型反应。相比之下，从免疫的野生型小鼠收获的T细胞的抗原特异性增殖、IL-2和IFN-γ产生受到抑制。出乎意料的是，烧伤的TCR转基因小鼠免疫后观察到高死亡率。
我们的结果表明，烧伤对初始和抗原激活的CD4+ T细胞有不同影响，并可使初始CD4+ T细胞致敏。
