A small case-control study determined that aging HIV-infected people (median 56 years) with a good CD4 count (median 724 cells/mm (3)) and long-term viral suppression with antiretroviral therapy have CD4 and CD8 cells
similar to those of a substantially older HIV-negative comparison group (median 88 years) and utterly unlike those of a younger HIV-negative group (median 27 years).
The CD8 cells
of long-term nonprogressors produce more perforin than do CD8 cells
of HIV-positive people who developed AIDS, the scientists found.
These findings undermine the current belief that, with HIV infection, both CD8 cells
and CD4 cells die and undergo a rapid turnover in the body, according to the researchers.
For people infected with HIV, the study reinforces the push for early treatment to hold down the amount of virus and thereby conserve CD8 cells
, Giorgi said.
The team also found that SIV creates such mutants in response to the assault by CD8 cells
at about the same rate as HIV does.
These are CD4 cell factors that are necessary to turn on the CD8 cells
(cytotoxic T lymphocytes).
Three research groups now challenge that dogma with evidence showing that under certain conditions, CD8 cells
can make the CD4 protein and consequently become infected by the AIDS virus.
TAT0002 was previously shown to stimulate the production of IFN-gamma -- a molecule involved in the anti-viral response of cytotoxic CD8 T-cells specific for the HIV-1 AIDS virus -- and to enhance the ability of the CD8 cells
to proliferate and kill HIV-1-infected CD4 cells.
The engineered stem cells developed into a large population of mature, multifunctional HIV-specific CD8 cells
that could specifically target cells containing HIV proteins.
Preliminary results suggest that both the CD4 and CD8 cells
appear to be multifunctional T cells, similar to the type that has recently been associated with protective responses.
Levy and others quickly established that CD8 cells
can secrete one or more soluble molecules that hinder HIV.
Effros and colleagues demonstrated that introducing the telomerase gene into CD8 cells
from HIV/AIDS donors increased: 1) their proliferative capacity, 2) their ability to produce IFN-gamma, and 3) their ability to inhibit virus production and kill HIV-infected T-cells.
They treated the CD8 T-cells with TAT2 and combined them with the CD4 T-cells in the dish-and found that the treated CD8 cells
inhibited production of HIV by the CD4 cells.
This "shut-down" of the CD8 cells
was evident in the tumors of the control (non-Multikine treated) group.
Populations of HIV-infected CD4 cells produced large amounts of HIV, whether they came from asymptomatic or late-stage AIDS patients, but adding CD8 cells
from long-term survivors or uninfected people shut down HIV production.