Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines

Emil P. Miskovsky, Alice Y. Liu, Wendy Pavlat, Renate Viveen, Patricia E. Stanhope, Diana Finzi, William M. Fox, Ralph H. Hruban, Eckhard R. Podack, Robert F. Siliciano

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Vaccine-induced, virus-specific CTLs may rapidly eliminate the host cells that first become infected after virus exposure, thereby preventing disseminated infection. Thus, there is much interest in the ability of candidate AIDS vaccines to elicit CTLs. All HIV-1 envelope (env) protein- based vaccines tested to date in seronegative humans induce CTLs from the CD4+ subset. Because the mechanism of cytolysis by CD4+ CTLs is controversial, a detailed study of the cytolytic reactions mediated by vaccine-induced, HIV-1-specific human CD4+ CTL clones was conducted. CD4+ CTL clones induced rapid destruction of Ag-pulsed target cells. Lysis was readily detectable within 15 min. Lysis was not a result of syncytium formation between CD4+ effector cells and env-expressing targets. Target cell destruction was not dependent upon de novo RNA or protein synthesis in either the effector or the target cell. Expression of perforin mRNA was detected by Northern blotting and reverse-transcriptase-PCR in CD4+ CTL clones but not in autologous B lymphoblastoid cell lines. Immunohistochemical studies demonstrated perforin protein in cytoplasmic granules in CD4+ CTL clones. Lysis by CD4+ CTLs was strictly dependent upon extracellular Ca2+ and was highly specific, with no lysis of innocent bystander cells. DNA fragmentation was detectable in target cells, but did not precede 51Cr release. Taken together, these results provide a dramatically different view of cytolysis by human CD4+ CTLs. Target cells are lysed by a rapid and efficient mechanism that involves a preformed mediator and that is functionally similar to the mechanism used by CD8+ CTLs.

Original languageEnglish
Pages (from-to)2787-2799
Number of pages13
JournalJournal of Immunology
Volume153
Issue number6
StatePublished - Sep 15 1994
Externally publishedYes

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AIDS Vaccines
HIV-1
Clone Cells
Perforin
Vaccines
Viruses
Cytoplasmic Granules
Proteins
DNA Fragmentation
Giant Cells
Reverse Transcriptase Polymerase Chain Reaction
Northern Blotting
RNA
Cell Line
Messenger RNA
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Miskovsky, E. P., Liu, A. Y., Pavlat, W., Viveen, R., Stanhope, P. E., Finzi, D., ... Siliciano, R. F. (1994). Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines. Journal of Immunology, 153(6), 2787-2799.

Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines. / Miskovsky, Emil P.; Liu, Alice Y.; Pavlat, Wendy; Viveen, Renate; Stanhope, Patricia E.; Finzi, Diana; Fox, William M.; Hruban, Ralph H.; Podack, Eckhard R.; Siliciano, Robert F.

In: Journal of Immunology, Vol. 153, No. 6, 15.09.1994, p. 2787-2799.

Research output: Contribution to journalArticle

Miskovsky, EP, Liu, AY, Pavlat, W, Viveen, R, Stanhope, PE, Finzi, D, Fox, WM, Hruban, RH, Podack, ER & Siliciano, RF 1994, 'Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines', Journal of Immunology, vol. 153, no. 6, pp. 2787-2799.
Miskovsky EP, Liu AY, Pavlat W, Viveen R, Stanhope PE, Finzi D et al. Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines. Journal of Immunology. 1994 Sep 15;153(6):2787-2799.
Miskovsky, Emil P. ; Liu, Alice Y. ; Pavlat, Wendy ; Viveen, Renate ; Stanhope, Patricia E. ; Finzi, Diana ; Fox, William M. ; Hruban, Ralph H. ; Podack, Eckhard R. ; Siliciano, Robert F. / Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines. In: Journal of Immunology. 1994 ; Vol. 153, No. 6. pp. 2787-2799.
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