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.
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 infectedpatients, 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.
Authors: Tobias M Nowacki; Stefanie Kuerten; Wenji Zhang; Carey L Shive; Christian R Kreher; Bernhard O Boehm; Paul V Lehmann; Magdalena Tary-Lehmann Journal: Cell Immunol Date: 2007-09-07 Impact factor: 4.868
Authors: Stefanie Kuerten; Robert J Asaad; Stephen P Schoenberger; Doychin N Angelov; Paul V Lehmann; Magdalena Tary-Lehmann Journal: AIDS Res Hum Retroviruses Date: 2008-09 Impact factor: 2.205
Authors: Kimberly A Shafer-Weaver; Thomas Sayers; Douglas B Kuhns; Susan L Strobl; Mark W Burkett; Michael Baseler; Anatoli Malyguine Journal: J Transl Med Date: 2004-09-20 Impact factor: 5.531