Okragly A J, Hanby-Flarida M, Baldwin C L
Department of Microbiology, Ohio State University, Columbus, USA.
Immunology. 1995 Dec;86(4):599-605.
Gamma-irradiated ex vivo bovine monocytes induce proliferation of gamma/delta T cells in the autologous mixed lymphocyte reaction (AMLR), whereas when not irradiated they prevent this response. In contrast, non-irradiated autologous monocytes have no effect on bovine alpha/beta T-cell proliferation in the allogenic MLR suggesting that the regulation is specific for gamma/delta T-cell responses. Here, we showed that the inhibition was not mediated by inducing cell death and that the ability of ex vivo monocytes to prevent proliferation of gamma/delta T cells was not generalized in that gamma/delta T cells still responded to mitogenic stimulation. Inhibition of the AMLR by non-irradiated monocytes could not be overcome by addition of interleukin-2 to the cultures or by costimulation with antibodies to WC1, a gamma/delta T-cell-specific cell-surface differentiation antigen shown elsewhere by us to be involved in activation of gamma/delta T cells. Furthermore, we showed that monocytes inhibited gamma/delta T-cell responses via a soluble product since inhibition occurred even when monocytes and gamma/delta T cells were separated by membranes of transwells or when supernatants from monocyte cultures were added to AMLR cultures. Maximal secretion of the inhibitory product by the monocytes occurred during the first 6 hr of in vitro culture at 37 degrees, rapidly decreased thereafter, and did not occur when monocytes were incubated at 4 degrees. The inhibition was not attributable to nitric oxide, reactive oxygen intermediates, prostaglandin E2 or transforming growth factor-beta (TGF-beta) but the ability of monocyte supernatants to mediate inhibition was sensitive to heating at 65 degrees. Lipopolysaccharide and granulocyte-macrophage colony-stimulating factor activation of monocytes temporarily abrogated their ability to inhibit proliferation. In contrast, heat-shocking had no effect on their ability to inhibit. We hypothesize that non-irradiated monocytes produce the inhibitory material in vivo in order to regulate gamma/delta T-cell responses to self-derived monocyte membrane components, but that when monocytes are altered by infection, transformation, irradiation, or cytokine activation, production of the inhibitor is temporarily suspended allowing stimulation of gamma/delta T cells to occur.
经γ射线照射的离体牛单核细胞在自体混合淋巴细胞反应（AMLR）中可诱导γ/δ T细胞增殖，而未经照射时则会抑制这种反应。相比之下，未经照射的自体单核细胞对同种异体混合淋巴细胞反应（MLR）中的牛α/β T细胞增殖没有影响，这表明这种调节对γ/δ T细胞反应具有特异性。在此，我们表明这种抑制作用不是通过诱导细胞死亡介导的，并且离体单核细胞阻止γ/δ T细胞增殖的能力并非普遍存在，因为γ/δ T细胞仍然对有丝分裂刺激有反应。向培养物中添加白细胞介素-2或用抗WC1抗体共刺激（WC1是一种γ/δ T细胞特异性细胞表面分化抗原，我们在其他地方已表明其参与γ/δ T细胞的激活），均无法克服未经照射的单核细胞对AMLR的抑制作用。此外，我们表明单核细胞通过一种可溶性产物抑制γ/δ T细胞反应，因为即使单核细胞和γ/δ T细胞被Transwell膜分隔开，或者将单核细胞培养物的上清液添加到AMLR培养物中，抑制作用仍然会发生。单核细胞在37℃体外培养的最初6小时内最大程度地分泌抑制性产物，此后迅速减少，而当单核细胞在4℃孵育时则不会分泌。这种抑制作用不归因于一氧化氮、活性氧中间体、前列腺素E2或转化生长因子-β（TGF-β），但单核细胞上清液介导抑制的能力对65℃加热敏感。脂多糖和粒细胞-巨噬细胞集落刺激因子激活单核细胞会暂时消除其抑制增殖的能力。相比之下，热休克对其抑制能力没有影响。我们推测，未经照射的单核细胞在体内产生抑制性物质，以调节γ/δ T细胞对自身来源的单核细胞膜成分的反应，但当单核细胞因感染、转化、照射或细胞因子激活而发生改变时，抑制剂的产生会暂时停止，从而允许γ/δ T细胞受到刺激。
