Human Tregs & sustained inhibition of CD8+ T cells & 12/03 EJI

More evidence that Tregs are the cause of the impaired HIV-specific
CD8+ T cell responses in HIV disease progression.

In the 12/03 European Journal of Immunology article titled "Human
CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T
cell activation," Camara et al. state:

"The experiments described here demonstrate that human CD4+CD25+ T cells
cause pronounced and sustained inhibition of CD8+ T cell proliferation
in response to polyclonal and allogeneic stimulation. The regulation of
CD8+ T cell activation was cell contact-dependent and included
inhibition of perforin, granzyme B and IFN-gamma cytokine production at
the transcriptional level and impaired cytotoxicity."

"One of the interesting features of the observed regulation was that the
effects on CD8+ T cells were sustained, beyond the time when CD4+CD25+ T
cells were physically present. . . . These results suggest that a form
of CD8+ T cell anergy is induced by stimulation in the presence of
CD4+CD25+ T cells. This may well have benefits in vivo, in that CD8+ T
cells whose initial activation was dampened by regulatory cells in
lymphoid tissue may be prevented from recovering full reactivity upon
entering an inflammatory environment in a peripheral tissue."

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Camara NO, Sebille F, Lechler RI. Human CD4+CD25+ regulatory cells have
marked and sustained effects on CD8+ T cell activation. Eur J Immunol.
2003 Dec;33(12):3473-83.

Department of Immunology, Division of Medicine, Imperial College London,
Hammersmith Hospital, London, GB. [EMAIL PROTECTED]

Abstract: Amongst the many types of regulatory cells that have been
described during the past few years, the spontaneously occurring
population that is characterized by co-expression of CD4 and CD25
appears to play a key role in the prevention of autoimmunity and the
maintenance of transplantation tolerance. In this study we have examined
the ability of CD4(+)CD25(+) T cells to regulate human CD8(+) T cells,
and the behavior of CD8(+) T cells following activation in the presence
of regulatory CD4(+)CD25(+) T cells. The experiments described here
demonstrate that human CD4(+)CD25(+) T cells cause pronounced and
sustained inhibition of CD8(+) T cell proliferation in response to
polyclonal and allogeneic stimulation. The regulation of CD8(+) T cell
activation was cell contact-dependent and included inhibition of
perforin, granzyme B and IFN-gamma cytokine production at the
transcriptional level and impaired cytotoxicity. The regulated CD8(+) T
cell population showed sustained hyporesponsiveness and refractoriness
to exogenous IL-2. These data provide insights into the short- and
long-term effects of CD4(+)CD25(+) T cells on CD8(+) T cells that could
be of considerable value in optimizing vaccination against tumor and
viral antigens.