Shearer G M, Salahuddin S Z, Markham P D, Joseph L J, Payne S M, Kriebel P, Bernstein D C, Biddison W E, Sarngadharan M G, Gallo R C
J Clin Invest. 1985 Oct;76(4):1699-704. doi: 10.1172/JCI112158.
Peripheral blood leukocytes (PBL) from 18 homosexual men who did not have acquired immunodeficiency syndrome (AIDS) and from 9 heterosexual men were repetitively tested for their ability to generate HLA self-restricted cytotoxic T lymphocyte responses to influenza virus (flu-self) over a 2-yr period. The sera of the same donors were tested for antibodies to human T lymphotropic virus-III (HTLV-III). Six of the homosexual and none of the heterosexual donors consistently generated weak cytotoxic T lymphocyte responses to flu-self. Seven of the homosexual and none of the heterosexual donors were seropositive for antibodies to HTLV-III. No obvious correlation was detected between weak flu-self cytotoxic T lymphocyte responses and antibodies to HTLV-III. However, one homosexual donor generated no detectable cytotoxic T lymphocyte activity to flu-self, although he was a strong responder to HLA-alloantigens. This donor had an OKT4:OKT8 ratio of 0.4 and was seropositive for HTLV-III antigens; HTLV-III virus was identified in his PBL; and he developed AIDS during the course of this study. A second donor with lymphadenopathy and who was seropositive for HTLV-III antigens exhibited marginal cytotoxic T lymphocyte activity to flu-self which he subsequently lost. PBL from two patients, one with Kaposi's sarcoma and one with generalized lymphadenopathy, were also tested for cytotoxic T lymphocyte responses to flu-self and to alloantigens. Both donors failed to generate cytotoxic T lymphocyte to flu-self, but generated strong cytotoxic T lymphocyte responses to alloantigens. The selective loss of an HLA-restricted cytotoxic T lymphocyte response without loss of HLA alloantigenic cytotoxic T lymphocyte activity may be an important functional immunologic characteristic in the development of AIDS.
在两年的时间里,对18名未患获得性免疫缺陷综合征(AIDS)的同性恋男性和9名异性恋男性的外周血白细胞(PBL)反复进行检测,以评估其产生针对流感病毒的HLA自身限制性细胞毒性T淋巴细胞反应(流感自身反应)的能力。检测了相同供体的血清中针对人类嗜T淋巴细胞病毒III型(HTLV-III)的抗体。6名同性恋供体始终产生较弱的针对流感自身的细胞毒性T淋巴细胞反应,而9名异性恋供体均未产生。7名同性恋供体的血清中HTLV-III抗体呈阳性,9名异性恋供体均为阴性。未检测到针对流感自身的弱细胞毒性T淋巴细胞反应与HTLV-III抗体之间存在明显相关性。然而,有一名同性恋供体,尽管他对HLA同种异体抗原反应强烈,但对流感自身却未检测到可检测的细胞毒性T淋巴细胞活性。该供体的OKT4:OKT8比值为0.4,HTLV-III抗原血清学呈阳性;在其外周血白细胞中鉴定出HTLV-III病毒;并且在本研究过程中他患上了艾滋病。另一名有淋巴结病且HTLV-III抗原血清学呈阳性的供体,对流感自身表现出微弱的细胞毒性T淋巴细胞活性,随后这种活性丧失。还检测了两名患者(一名患有卡波西肉瘤,一名患有全身性淋巴结病)的外周血白细胞对流感自身和同种异体抗原的细胞毒性T淋巴细胞反应。两名供体均未产生针对流感自身的细胞毒性T淋巴细胞,但对同种异体抗原产生了强烈的细胞毒性T淋巴细胞反应。HLA限制性细胞毒性T淋巴细胞反应选择性丧失而HLA同种异体抗原细胞毒性T淋巴细胞活性未丧失,可能是艾滋病发展过程中的一个重要功能性免疫特征。