Gauduin M C, Glickman R L, Means R, Johnson R P
Divisions of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
J Virol. 1998 Aug;72(8):6315-24. doi: 10.1128/JVI.72.8.6315-6324.1998.
Characterization of immune responses induced by live attenuated simian immunodeficiency virus (SIV) strains may yield clues to the nature of protective immunity induced by this vaccine approach. We investigated the ability of CD8(+) T lymphocytes from rhesus macaques immunized with the live, attenuated SIV strain SIVmac239Deltanef or SIVmac239Delta3 to inhibit SIV replication. CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells. Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted. However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold. Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains. Stimulation of CD8(+) cells with cognate cytotoxic T-lymphocyte epitopes also induced secretion of soluble factors able to inhibit SIV replication. Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals. However, addition of antibodies that neutralize these beta-chemokines, either alone or in combination, only partly blocked inhibition of SIV and HIV replication by soluble factors produced by stimulated CD8(+) T cells. Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
减毒活猴免疫缺陷病毒（SIV）株诱导的免疫反应特征可能为这种疫苗方法诱导的保护性免疫的本质提供线索。我们研究了用减毒活SIV株SIVmac239Deltanef或SIVmac239Delta3免疫的恒河猴的CD8(+) T淋巴细胞抑制SIV复制的能力。来自免疫动物的CD8(+) T淋巴细胞能够有效抑制自体SIV感染的CD4(+) T细胞中的SIV复制。未刺激的CD8(+) T细胞对SIV复制的抑制需要直接接触，并且受主要组织相容性复合体（MHC）限制。然而，CD3刺激的CD8(+) T细胞产生的可溶性因子以MHC非限制方式抑制SIV复制的能力高达30倍。刺激的CD8(+) T细胞的上清液也能够抑制CCR5和CXCR4依赖的1型人类免疫缺陷病毒（HIV-1）株的复制。用同源细胞毒性T淋巴细胞表位刺激CD8(+)细胞也诱导了能够抑制SIV复制的可溶性因子的分泌。接种疫苗动物的刺激CD8(+) T细胞产生的调节激活正常T细胞表达和分泌因子（RANTES）、巨噬细胞炎性蛋白1α（MIP-1α）或MIP-1β比对照动物刺激的CD8(+) T细胞高近10倍。然而，单独或联合添加中和这些β趋化因子的抗体仅部分阻断了刺激的CD8(+) T细胞产生的可溶性因子对SIV和HIV复制的抑制。我们的结果表明，用减毒活SIV株免疫的动物的CD8(+) T细胞对SIV复制的抑制涉及MHC限制和非限制机制，并且MHC非限制的SIV复制抑制主要归因于RANTES、MIP-1α和MIP-1β以外的可溶性因子。
