Mann D L, Gartner S, Le Sane F, Buchow H, Popovic M
Laboratory of Viral Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20895.
J Immunol. 1990 Mar 15;144(6):2152-8.
Monocyte/macrophages (MM) were isolated from HIV-1 seronegative individuals, infected with HIV-1 and examined for their ability to infect autologous T lymphocytes with and without concomitant presentation of exogenous Ag. HIV-1-infected MM presented tetanus toxin (TT) and streptokinase to T cells (as measured by [3H]thymidine incorporation) comparable to presentation by uninfected MM. In these studies, it was observed that HIV-1-infected MM without additional exogenous Ag stimulated autologous T lymphocytes, however, to a lesser degree than with TT and streptokinase. Virus production in T cells appeared to be relative to the degree of stimulation with the highest levels of stimulation and infection observed when T cells were exposed to HIV-1-infected TT-presenting MM. Studies were carried out to examine some of the restricting elements in MM-mediated infection of T lymphocytes with and without TT presentation. Antibodies to CD4, as well as soluble immunopurified gp120, blocked cell-mediated infection indicating that infection of T cells was through the CD4 molecule as has been demonstrated with cell-free virus. In addition, soluble gp120 inhibited Ag presentation by HIV-1-infected and uninfected MM. mAb to MHC class II Ag HLA-DR and -DP blocked T cell infection by HIV-1-infected MM with and without presentation of TT. No effect was observed with mAb to MHC class I Ag. These results indicate that virus transmission to T lymphocytes can be mediated by HIV-1-infected MM and that these cells maintain their function as APC. Activation of T cells appears to be important in the process of T cell infection in this system inasmuch as antibodies that block Ag presentation and thus a T cell proliferative signal inhibit infection.
单核细胞/巨噬细胞（MM）从HIV-1血清阴性个体中分离出来，感染HIV-1，并检测其在有或无外源性抗原同时存在的情况下感染自体T淋巴细胞的能力。HIV-1感染的MM向T细胞呈递破伤风毒素（TT）和链激酶（通过[3H]胸腺嘧啶核苷掺入法测定），其能力与未感染的MM相当。在这些研究中，观察到未添加额外外源性抗原的HIV-1感染的MM刺激自体T淋巴细胞，但程度低于添加TT和链激酶时。T细胞中的病毒产生似乎与刺激程度相关，当T细胞暴露于HIV-1感染的呈递TT的MM时，观察到最高水平的刺激和感染。开展研究以检查MM介导的T淋巴细胞感染（有或无TT呈递）中的一些限制因素。抗CD4抗体以及可溶性免疫纯化的gp120阻断了细胞介导的感染，表明T细胞感染是通过CD4分子进行的，这已在无细胞病毒的情况下得到证实。此外，可溶性gp120抑制HIV-1感染和未感染的MM的抗原呈递。针对MHC II类抗原HLA-DR和-DP的单克隆抗体阻断了HIV-1感染的MM对T细胞的感染，无论有无TT呈递。针对MHC I类抗原的单克隆抗体未观察到效果。这些结果表明，HIV-1感染的MM可介导病毒向T淋巴细胞的传播，并且这些细胞保持其作为抗原呈递细胞的功能。在该系统中，T细胞感染过程中T细胞的激活似乎很重要，因为阻断抗原呈递从而阻断T细胞增殖信号的抗体抑制感染。
