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In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.

Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, Ignacio CC, Russell T, Pillai SK, Looney DJ, Dandekar S - PLoS Pathog. (2010)

Bottom Line: The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms.As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication.These observations have important implications for future strategies to augment immune control of HIV.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.

ABSTRACT
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.

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Related in: MedlinePlus

CD8 T-cell concentrations before, following treatment with cMT-807 antibody and after starting PMPA/FTC.Results are displayed separately for full depletion, partial depletion and control animals. Time scales differ for each epoch shown and the x-axes are not to scale.
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ppat-1000748-g003: CD8 T-cell concentrations before, following treatment with cMT-807 antibody and after starting PMPA/FTC.Results are displayed separately for full depletion, partial depletion and control animals. Time scales differ for each epoch shown and the x-axes are not to scale.

Mentions: After 12 weeks of SIV infection, CD4 T-cell counts in whole blood declined from a median of 807 to 693 cells/mm3 and CD8+ T-cells rose from 612 to 1247 cells/mm3 (Figures 3, 4). There were no significant differences between control and study animals in set point VL, CD4% and CD8% prior to administration of the CD8+ T-cell depleting antibody (Table 1). To the degree that these parameters reflected the equilibrium between pathologic effects of viral replication and effects of host immune response, the animals in the control and treatment arms of the study appeared comparable.


In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells.

Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, Ignacio CC, Russell T, Pillai SK, Looney DJ, Dandekar S - PLoS Pathog. (2010)

CD8 T-cell concentrations before, following treatment with cMT-807 antibody and after starting PMPA/FTC.Results are displayed separately for full depletion, partial depletion and control animals. Time scales differ for each epoch shown and the x-axes are not to scale.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2813272&req=5

ppat-1000748-g003: CD8 T-cell concentrations before, following treatment with cMT-807 antibody and after starting PMPA/FTC.Results are displayed separately for full depletion, partial depletion and control animals. Time scales differ for each epoch shown and the x-axes are not to scale.
Mentions: After 12 weeks of SIV infection, CD4 T-cell counts in whole blood declined from a median of 807 to 693 cells/mm3 and CD8+ T-cells rose from 612 to 1247 cells/mm3 (Figures 3, 4). There were no significant differences between control and study animals in set point VL, CD4% and CD8% prior to administration of the CD8+ T-cell depleting antibody (Table 1). To the degree that these parameters reflected the equilibrium between pathologic effects of viral replication and effects of host immune response, the animals in the control and treatment arms of the study appeared comparable.

Bottom Line: The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms.As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication.These observations have important implications for future strategies to augment immune control of HIV.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.

ABSTRACT
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.

Show MeSH
Related in: MedlinePlus