Qiao L, Schürmann G, Betzler M, Meuer S C
Department of Applied Immunology, University of Heidelberg, FRG.
Eur J Immunol. 1991 Oct;21(10):2385-9. doi: 10.1002/eji.1830211014.
Human lamina propria T lymphocytes (LPL-T) were shown to have lower proliferative responses to CD3 triggering than autologous peripheral blood T lymphocytes (PBL-T), yet preserved their responsiveness to CD2 stimulation. In order to elucidate the basis of these differences, freshly recovered human LPL-T and autologous PBL-T were stimulated with CD2 monoclonal antibodies anti-T11(2/3) plus sheep red blood cells and phorbol 12,13-dibutyrate (PBu2) plus ionomycin, respectively. LPL-T showed invariably lower responses to PBu2 plus ionomycin than PBL-T. In contrast, LPL-T still preserved proliferation to CD2 activation even when their responses to PBu2 plus ionomycin were decreased almost to background levels. Preincubation of PBL-T with intestinal mucosa supernatant led to a similar reactivity as observed in fresh LPL-T. Moreover, the protein kinase C (PKC) inhibitor sphinganine was able to inhibit DNA synthesis to stimulation with PBu2 plus ionomycin but not to CD2 triggering. This study suggests that CD2-induced proliferation is not dependent on PKC activation and that down-regulation of PKC activation may be one of the mechanisms for inhibition of the CD3-Ti-dependent activation pathway in LPL-T by intestinal mucosa-derived influences in vivo.
人固有层T淋巴细胞（LPL-T）对CD3触发的增殖反应低于自体外周血T淋巴细胞（PBL-T），但其对CD2刺激的反应性得以保留。为阐明这些差异的基础，分别用抗T11(2/3)的CD2单克隆抗体加绵羊红细胞以及佛波醇12,13 - 二丁酸酯（PBu2）加离子霉素刺激新鲜分离的人LPL-T和自体PBL-T。LPL-T对PBu2加离子霉素的反应始终低于PBL-T。相反，即使LPL-T对PBu2加离子霉素的反应几乎降至背景水平，其对CD2激活仍保留增殖能力。用肠黏膜上清液预孵育PBL-T可导致与新鲜LPL-T中观察到的类似反应性。此外，蛋白激酶C（PKC）抑制剂鞘氨醇能够抑制对PBu2加离子霉素刺激的DNA合成，但不能抑制对CD2触发的反应。本研究表明，CD2诱导的增殖不依赖于PKC激活，PKC激活的下调可能是体内肠黏膜衍生影响抑制LPL-T中CD3-Ti依赖性激活途径的机制之一。
