Reposted - obvious the apologists can't comprehend the
BASIC SCIENCE...

It's all about Tregs.

"Interestingly, in both human immunodeficiency virus and hepatitis C
 virus infection CD4+ regulatory T cells have been described to
 suppress antiviral T-cell responses. Thus, impairment of CD8+ T-cell
 function via regulatory T cells may be a mechanism contributing to
 virus escape and the establishment of chronic infections."

In the 8/15/05 Journal of Virology article titled "CD8+ T-Cell
Dysfunction due to Cytolytic Granule Deficiency in Persistent Friend
Retrovirus Infection," Zelinskyy et al. state:

"The current study extends the results from these adoptive transfer
experiments to the endogenous population of FV-specific CD8+ T cells
and investigates the defects at the molecular level. All three of the
major molecules involved in cytotoxicity were analyzed: perforin,
granzyme A, and granzyme B. The results showed deficiencies in all
three proteins compared to CD8+ T cells from acutely infected mice.
Interestingly, the regulation of protein expression varied from
protein to protein, with only granzyme B being regulated at the
transcriptional level. These results suggest the possibility that
multiple upstream signals control cytotoxic granule content."

"Functional impairment of CD8+ T cells has been described for patients
infected with human immunodeficiency virus and in patients with
hepatitis C virus. Both viruses are genetically highly variable and
escape from CD8+ T-cell responses by mutations in T-cell epitopes has
been discussed as a major reason for the loss of CD8+ T-cell activity
in chronic infected carriers. However, other evidence suggests that
several viral epitopes of human immunodeficiency virus and hepatitis C
virus are recognized by CD8+ T cells throughout the chronic phase of
infection and that viral loads in infected patients are more
associated with functional properties of CD8+ T cells than with viral
mutations.

Interestingly, in both human immunodeficiency virus and hepatitis C
virus infection CD4+ regulatory T cells have been described to
suppress antiviral T-cell responses. Thus, impairment of CD8+ T-cell
function via regulatory T cells may be a mechanism contributing to
virus escape and the establishment of chronic infections.

"It is likely that suppression of cytotoxic T-lymphocyte function has
evolved as a mechanism to control the immunopathological damage that
can occur as a consequence of cytolytic killing by CD8+ T cells. For
example, in the mouse model for hepatitis B infection CD8+ T cells
exhibit virus control via gamma interferon and tumor necrosis factor
alpha production without causing the liver tissue destruction that
would result from active cytolysis. In human immunodeficiency virus
infections, the down-regulation of perforin in virus-specific CD8+ T
cells from gut-associated lymphoid tissue may be a mechanism to
protect the integrity of the rectal mucosa from cytotoxic T-lymphocyte
activity. The role of regulatory T cells in dampening cytolytic
activity may have evolved as a control over immunopathology. For
example, it has been shown that the immunopathological damage caused
by herpes simplex virus infections of the eye is significantly more
severe in the absence of regulatory T cells. Thus, suppression of
cytolytic activity during persistent infections may represent a host
compromise between the immunopathological damage that could accompany
complete elimination of infection, and the pathological damage
associated with the persistent virus. For most persistent viruses the
compromise is probably beneficial to the host, but for notable
exceptions such as hepatitis C virus and human immunodeficiency virus,
the consequences can be lethal.

"We have now identified broad impairment of CD8+ T-cell effector
functions during persistent FV infection, including reduced gamma
interferon secretion and reductions in all three major cytotoxic
molecules: perforin, granzyme A, and granzyme B. It may be necessary
to down-regulate all three cytotoxic molecules because previous
results indicated that deficiency in one or even two of them was not
sufficient to prevent CD8+ T-cell function in FV infection. The
finding that the down-regulation of granzyme B appeared to be in part
at the level of transcription while the regulation of both perforin
and granzyme A appeared posttranscriptional indicates complex
regulatory mechanisms. The elucidation of these mechanisms could lead
to new therapeutic approaches to specifically reactivate CD8+ T-cell
functions for the reduction or clearance of chronic viral infections."

------------------------------------------------------------------------

Zelinskyy G. Robertson SJ, Schimmer S, Messer RJ, Hasenkrug KJ,
Dittmer U. CD8+ T-Cell Dysfunction due to Cytolytic Granule Deficiency
in Persistent Friend Retrovirus Infection. J Virol 2005 Aug
15;79:10619-10626.

Institut fuer Virologie des Universitaetsklinikums Essen, Essen,
Germany Email: ulf.dittmer@uni-essen.de

Abstract: Virus-specific CD8+ T cells are critical for the control of
acute Friend virus (FV) infections, but are rendered impotent by CD4+
regulatory T cells during the chronic phase of infection. The current
study examines this CD8+ T-cell dysfunction by analyzing the
production and release of cytolytic molecules by CD8+ T cells. CD8+ T
cells with an activated phenotype (CD43+) from acutely infected mice
produced all three key components of lytic granules: perforin,
granzyme A, and granzyme B. Furthermore, they displayed evidence of
recent degranulation and in vivo cytotoxicity. In contrast, activated
CD8+ T cells from chronically infected mice were deficient in
cytolytic molecules and showed little evidence of recent degranulation
and poor in vivo cytotoxicity. Evidence from tetramer-positive CD8+ T
cells with known virus specificity confirmed the findings from the
activated subset of CD8+ T cells. Interestingly, perforin and granzyme
A mRNA levels were not significantly reduced during chronic infection,
indicating control at a posttranscriptional level. Granzyme B
deficiency was associated with a significant decrease in mRNA levels,
but posttranscriptional control also appeared to contribute to
deficiency. These results demonstrate a broad impairment of cytotoxic
CD8+ T-cell effector function during chronic retroviral infection and
explain the inability of virus-specific CD8+ T cells to eliminate
persistent virus.