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AIDS. 2004 Feb 20;18(3):383-92.

Tc1 effector diversity shows dissociated expression of granzyme B and interferon-gamma in HIV infection.

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1
Department of Pathology and the Center for AIDS research, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Abstract

OBJECTIVE:

To examine antigen specific cytotoxic effector T cell diversity in HIV infected individuals.

DESIGN:

We used a panel of previously defined HLA class I-restricted HIV peptides to stimulate CD8 cells in freshly isolated peripheral blood mononuclear cells of HIV infected patients, to determine cognate killing via the perforin-granzyme pathway and inflammation induced by secretion of interferon (IFN)-gamma.

METHODS:

ELISPOT assays were used to measure the secretion of granzyme B (GzB) and IFN-gamma at single cell resolution.

RESULTS:

In all nine patients only approximately 20% of the peptides triggered a canonical Tc1 response with simultaneous release of GzB and IFN-gamma. The majority of these peptides (approximately 80%) that elicited recall responses fell into the 'single positive' category with induction of either GzB or IFN-gamma alone. The GzB positive cells did not produce interleukin (IL)-4 or IL-5.

CONCLUSION:

The GzB positive but IFN-gamma negative CD8 cells are programmed to induce apoptosis mediated killing without inflammation while the GzB negative and IFN-gamma positive CD8 cells could mediate inflammation without killing. This Tc1 CD8 effector cell diversity and the understanding of these differentiation mechanisms may enable the precise implementation and fine-tuning of fundamentally different defense strategies against HIV and other infections.

PMID:
15090789
[Indexed for MEDLINE]
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