Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection: Humoral and cellular defects

Douglas Tyler, S. David Stanley, Chet A. Nastala, Arthur A. Austin, John A. Bartlett, Kimo C. Stine, H. Kim Lyerly, Dani P. Bolognesi, Kent J. Weinhold

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Abstract

HIV-1-specific cell-mediated cytotoxicity (CMC) is a form of antibody-dependent cellular cytotoxicity (ADCC) in which HIV-1-specific antibodies arm NK cells directly to become cytotoxic for targets bearing HIV-1 antigenic determinants. This non-MHC-restricted cytotoxic activity is present in early stages of disease and declines markedly with disease progression. To understand the cellular and humoral factors contributing to the reduction in this activity, the conditions under which maximal arming of cells occurs was examined in vitro. With the use of a large patient cohort, a strong positive correlation was found between the capacity of a serum to direct lysis in standard ADCC assays and its ability to arm NK cells. Patients with minimal HTV-1-specific ADCC-directing antibodies exhibited low levels of CMC and were unable to arm normal effector cells in vitro. The lack of sufficient ADCC-directing antibodies was found to be one cause of defective CMC in some patients. Unlike asymptomatics, only a weak positive correlation was found between arming and ADCC with sera from AIDS patients, indicating that a factor other than absolute HIV-1 specific antibody titer was responsible for decreased CMC in this patient population. Another group of patients was found to have diminished CMC despite the presence of antibodies in the serum that were fully capable of arming normal effector cells to become cytotoxic for gp120-expressing targets. When compared with those of normal individuals, lymphocytes from seropositive patients mediated significantly reduced levels of cytotoxicity in ADCC and arming assays with the use of a high titered HIV-1-specific serum. In both assay systems, the magnitude and frequency of dysfunction in antibody-dependent cytolysis was found to greater among AIDS patients than among asymptomatic individuals. The demonstration of both cellular and humoral defects in the ability of seropositive individuals to manifest ADCC reactivities strongly suggests that HIV-1 infection may significantly compromise the effectiveness of this potentially important cytolytic reactivity in vivo.

Original languageEnglish (US)
Pages (from-to)3375-3384
Number of pages10
JournalJournal of Immunology
Volume144
Issue number9
StatePublished - May 1 1990
Externally publishedYes

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HIV Infections
HIV-1
Antibodies
Serum
Natural Killer Cells
Acquired Immunodeficiency Syndrome
Disease Progression
Epitopes
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Tyler, D., Stanley, S. D., Nastala, C. A., Austin, A. A., Bartlett, J. A., Stine, K. C., ... Weinhold, K. J. (1990). Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection: Humoral and cellular defects. Journal of Immunology, 144(9), 3375-3384.

Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection : Humoral and cellular defects. / Tyler, Douglas; Stanley, S. David; Nastala, Chet A.; Austin, Arthur A.; Bartlett, John A.; Stine, Kimo C.; Lyerly, H. Kim; Bolognesi, Dani P.; Weinhold, Kent J.

In: Journal of Immunology, Vol. 144, No. 9, 01.05.1990, p. 3375-3384.

Research output: Contribution to journalArticle

Tyler, D, Stanley, SD, Nastala, CA, Austin, AA, Bartlett, JA, Stine, KC, Lyerly, HK, Bolognesi, DP & Weinhold, KJ 1990, 'Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection: Humoral and cellular defects', Journal of Immunology, vol. 144, no. 9, pp. 3375-3384.
Tyler, Douglas ; Stanley, S. David ; Nastala, Chet A. ; Austin, Arthur A. ; Bartlett, John A. ; Stine, Kimo C. ; Lyerly, H. Kim ; Bolognesi, Dani P. ; Weinhold, Kent J. / Alterations in antibody-dependent cellular cytotoxicity during the course of HIV-1 infection : Humoral and cellular defects. In: Journal of Immunology. 1990 ; Vol. 144, No. 9. pp. 3375-3384.
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abstract = "HIV-1-specific cell-mediated cytotoxicity (CMC) is a form of antibody-dependent cellular cytotoxicity (ADCC) in which HIV-1-specific antibodies arm NK cells directly to become cytotoxic for targets bearing HIV-1 antigenic determinants. This non-MHC-restricted cytotoxic activity is present in early stages of disease and declines markedly with disease progression. To understand the cellular and humoral factors contributing to the reduction in this activity, the conditions under which maximal arming of cells occurs was examined in vitro. With the use of a large patient cohort, a strong positive correlation was found between the capacity of a serum to direct lysis in standard ADCC assays and its ability to arm NK cells. Patients with minimal HTV-1-specific ADCC-directing antibodies exhibited low levels of CMC and were unable to arm normal effector cells in vitro. The lack of sufficient ADCC-directing antibodies was found to be one cause of defective CMC in some patients. Unlike asymptomatics, only a weak positive correlation was found between arming and ADCC with sera from AIDS patients, indicating that a factor other than absolute HIV-1 specific antibody titer was responsible for decreased CMC in this patient population. Another group of patients was found to have diminished CMC despite the presence of antibodies in the serum that were fully capable of arming normal effector cells to become cytotoxic for gp120-expressing targets. When compared with those of normal individuals, lymphocytes from seropositive patients mediated significantly reduced levels of cytotoxicity in ADCC and arming assays with the use of a high titered HIV-1-specific serum. In both assay systems, the magnitude and frequency of dysfunction in antibody-dependent cytolysis was found to greater among AIDS patients than among asymptomatic individuals. The demonstration of both cellular and humoral defects in the ability of seropositive individuals to manifest ADCC reactivities strongly suggests that HIV-1 infection may significantly compromise the effectiveness of this potentially important cytolytic reactivity in vivo.",
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