Tc1 effector diversity shows dissociated expression of granzyme B and interferon-gamma in HIV infection.
OBJECTIVE
To examine antigen specific cytotoxic effector T cell diversity in HIV infected individuals.


METHODS
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.


CONCLUSIONS
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.
Kleen
Thomas O
TO
Department of Pathology and the Center for AIDS research, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Asaad
Robert
R
Landry
Samuel J
SJ
Boehm
Bernhard O
BO
Tary-Lehmann
Magdalena
M
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005805:Genes, MHC Class I / Q000276:immunology; D053804:Granzymes; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015488:HIV Antigens; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases