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1996-02-26
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Document 0602
DOCN M9620602
TI Th1 cells specific for HIV-1 gag p24 are less efficient than Th0 cells
in supporting HIV replication, and inhibit virus replication in Th0
cells.
DT 9602
AU Vyakarnam A; Matear PM; Martin SJ; Wagstaff M; Department of Immunology,
University College London Medical; School, UK.
SO Immunology. 1995 Sep;86(1):85-96. Unique Identifier : AIDSLINE
MED/96091076
AB This report provides three lines of evidence to suggest that T-helper
type 1 (Th1) and type 0 (Th0) cells could play an opposing role in
acquired immune deficiency syndrome (AIDS). Using a panel of Th1 and Th0
clones specific for human immunodeficiency virus-1 (HIV-1) gag p24,
derived from seronegative volunteers immunized with gag p24: Ty
virus-like particles, a Th1 clone specific for tuberculin (PPD), and a
Th0 clone derived by random activation from the same volunteer, we have
demonstrated the following differences in the capacity of these clones
to regulate the in vitro replication of HIV. (1) Th1 clones were less
efficient than Th0 clones in supporting HIV replication, both in their
resting state (by 10-1000-fold) and after antigen activation (by five to
100-fold). Furthermore, the infectious titre of HIV recovered from the
Th0 population was more than 1000-fold higher than virus from the Th1
population, and the number of HIV-infected Th0 cells was five to 16
times higher than the number of infected Th1 cells. (2) Antigen- or
mitogen-activated Th1, but not Th0 clones, inhibited HIV in bystander
CEM-4 cells. Th1 cells also inhibited HIV in autologous and allogeneic
Th0 cells. The level of inhibition in these experiments ranged from 50%
to 100% and was three to 10-fold higher and more sustained in the
presence of p24-specific clones compared to the PPD-specific Th1 clone.
The capacity of Th1 cells to inhibit HIV in neighbouring cells was also
reflected in the reduced replication of HIV in the clones immediately
after antigen activation compared to unstimulated cells. Kinetic studies
of virus production, cytokine release and proliferation showed that
inhibition of HIV was associated with peak cytokine release and
preceeded proliferation. (3) The Th1 clones had higher cytolytic
potential than the Th0 clones. Therefore, the HIV inhibitory activity of
Th1 cells could be partly due to cell to cell killing. These data
demonstrate the opposing effects of Th1 and Th0 cells on the in vitro
replication of HIV, and suggest that Th1 cells might be important in
immunity whereas Th0/Th2 cells might lay a role in promoting disease.
DE Clone Cells CD4-Positive T-Lymphocytes/*IMMUNOLOGY/VIROLOGY Human HIV
Core Protein p24/*IMMUNOLOGY HIV-1/IMMUNOLOGY/*PHYSIOLOGY Interferon
Type II/METABOLISM Interleukin-2/METABOLISM Interleukin-4/METABOLISM
Lymphocyte Transformation Support, Non-U.S. Gov't Th1
Cells/*IMMUNOLOGY/VIROLOGY Virus Replication/*IMMUNOLOGY JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).