Ennen J, Findeklee H, Dittmar M T, Norley S, Ernst M, Kurth R
Paul-Ehrlich Institute, Langen, Germany.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7207-11. doi: 10.1073/pnas.91.15.7207.
Following natural and experimental infection by simian immunodeficiency virus SIVagm of African green monkeys (AGMs), the natural host, there is no evidence for the development of an immunodeficiency. Within the framework of our studies on human immunodeficiency virus (HIV)/SIV pathogenesis, we investigated the influence of CD8 T lymphocytes on SIVagm replication in AGM CD4 T lymphocytes in vitro. The following observations were made: (i) Peripheral blood mononuclear cells from both seronegative and seropositive AGMs contained only a low proportion (i.e., 10%) of CD4+ lymphocytes, whereas a high proportion (80%) of CD8+ cells was detected. Even after persistent SIVagm infection, CD4 T lymphocytes do not decrease in number. (ii) The target of in vitro infection of peripheral blood cells is the CD4+ mononuclear cell (T lymphocytes, monocytes) and SIVagm infects by binding to the CD4 molecule. (iii) In both naturally and experimentally SIVagm-infected AGMs the CD4+ T cells and monocytes, but not the CD8+ T cells, harbor DNA provirus. (iv) Virus reisolation and virus replication of SIVagm in CD4 T lymphocytes from seropositive AGMs is suppressed in the presence of autologous CD8 T lymphocytes or a soluble factor produced by these cells. Taken together, one possible reason for the apathogenicity of the SIVagm infection in AGMs may be the suppression of virus replication by a soluble, yet unidentified factor secreted by CD8 lymphocytes quantitatively dominating among peripheral blood cell populations. We have tentatively termed this factor "immunodeficiency virus-suppressing lymphokine." In addition, we show that immunodeficiency virus-suppressing lymphokine from AGMs is able to suppress HIV-1 replication in human CD4+ T cells.
在非洲绿猴（AGM）这一自然宿主受到猿猴免疫缺陷病毒SIVagm的自然感染和实验感染后，没有证据表明会出现免疫缺陷。在我们关于人类免疫缺陷病毒（HIV）/SIV发病机制的研究框架内，我们在体外研究了CD8 T淋巴细胞对AGM CD4 T淋巴细胞中SIVagm复制的影响。得到了以下观察结果：（i）来自血清阴性和血清阳性AGM的外周血单核细胞中仅含有低比例（即10%）的CD4+淋巴细胞，而检测到高比例（80%）的CD8+细胞。即使在持续的SIVagm感染后，CD4 T淋巴细胞的数量也不会减少。（ii）外周血细胞体外感染的靶细胞是CD4+单核细胞（T淋巴细胞、单核细胞），并且SIVagm通过与CD4分子结合进行感染。（iii）在自然感染和实验感染SIVagm的AGM中，CD4+ T细胞和单核细胞而非CD8+ T细胞含有DNA原病毒。（iv）在自体CD8 T淋巴细胞或这些细胞产生的可溶性因子存在的情况下，血清阳性AGM的CD4 T淋巴细胞中SIVagm的病毒再分离和病毒复制受到抑制。综上所述，SIVagm感染AGM无致病性的一个可能原因可能是CD8淋巴细胞分泌的一种可溶性但尚未明确的因子对病毒复制的抑制，在外周血细胞群体中CD8淋巴细胞在数量上占主导。我们暂时将这种因子称为“免疫缺陷病毒抑制性淋巴因子”。此外，我们表明来自AGM的免疫缺陷病毒抑制性淋巴因子能够抑制HIV-1在人CD4+ T细胞中的复制。
