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GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody.

Publication ,  Journal Article
Tyler, DS; Nastala, CL; Stanley, SD; Matthews, TJ; Lyerly, HK; Bolognesi, DP; Weinhold, KJ
Published in: J Immunol
February 15, 1989

Fresh circulating PBMC from HIV-1 seropositive individuals have been found to mediate specific, non-MHC restricted lysis of targets expressing the major envelope glycoprotein of HIV-1, gp120, in 6-h 51Cr release assays. This gp120 specific cell-mediated cytotoxicity (CMC) is broadly reactive against target cells infected with a wide range of viral isolates, is IL-2 augmentable, and is mediated by a CD16+, Leu-7+, CD15-, CD3- population of NK/K cells. The presence of FcR (CD16) on these cells suggested that the lytic specificity for gp120 might be directed by cytophilic antibody bound to the cell surface. Affinity purified F(ab')2 antibody fragments specific for the Fc and F(ab')2 portions of human IgG were used in attempts to block gp120 specific lysis. A 1/50 dilution of these antibodies inhibited gp120 specific cytolytic activity by more than 90% while exhibiting a minimal effect on NK/K cell lysis of K562 targets. The blocking activity of these fragments demonstrates the direct involvement of cytophilic antibody in CMC. In attempts to isolate this cytophilic anti-HIV-1 antibody, short 56 degrees C incubations were used to dissociate antibodies from the surface of PBMC of seropositive individuals. The supernatants generated in this manner exhibited specific gp120 activity in antibody-dependent cellular cytotoxicity assays. The ability of Staphylococcal protein A to remove this activity confirms the presence of cytophilic antibody on freshly isolated PBMC. Selective enrichment of specific cell subpopulations revealed the origin of the cytophilic antibody to be CD16+ NK/K cells and not B cells, T cells, or monocytes/macrophages. These studies show that the gp120-specific CMC seen in HIV-1 seropositive individuals is directed by cytophilic antibody bound to circulating CD16+ NK/K cells and represents a form of direct antibody-dependent cellular cytotoxicity which may provide a primary cytotoxic host defense.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

February 15, 1989

Volume

142

Issue

4

Start / End Page

1177 / 1182

Location

United States

Related Subject Headings

  • Retroviridae Proteins
  • Receptors, Fc
  • Killer Cells, Natural
  • Immunology
  • Humans
  • HIV-1
  • HIV Seropositivity
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Cell Separation
 

Citation

APA
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ICMJE
MLA
NLM
Tyler, D. S., Nastala, C. L., Stanley, S. D., Matthews, T. J., Lyerly, H. K., Bolognesi, D. P., & Weinhold, K. J. (1989). GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody. J Immunol, 142(4), 1177–1182.
Tyler, D. S., C. L. Nastala, S. D. Stanley, T. J. Matthews, H. K. Lyerly, D. P. Bolognesi, and K. J. Weinhold. “GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody.J Immunol 142, no. 4 (February 15, 1989): 1177–82.
Tyler DS, Nastala CL, Stanley SD, Matthews TJ, Lyerly HK, Bolognesi DP, et al. GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody. J Immunol. 1989 Feb 15;142(4):1177–82.
Tyler DS, Nastala CL, Stanley SD, Matthews TJ, Lyerly HK, Bolognesi DP, Weinhold KJ. GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody. J Immunol. 1989 Feb 15;142(4):1177–1182.

Published In

J Immunol

ISSN

0022-1767

Publication Date

February 15, 1989

Volume

142

Issue

4

Start / End Page

1177 / 1182

Location

United States

Related Subject Headings

  • Retroviridae Proteins
  • Receptors, Fc
  • Killer Cells, Natural
  • Immunology
  • Humans
  • HIV-1
  • HIV Seropositivity
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Cell Separation