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Functional impairment of central memory CD4 T cells is a potential early prognostic marker for changing viral load in SHIV-infected rhesus macaques.

He H, Nehete PN, Nehete B, Wieder E, Yang G, Buchl S, Sastry KJ - PLoS ONE (2011)

Bottom Line: Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4(+) T cells, but not CD8(+) T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation.Highly viremic animals showed impaired cytokine-production by all T cells subsets.These results suggest that functional impairment of CD4(+) T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.

ABSTRACT
In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4(+) T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4(+) T cells, but not CD8(+) T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4(+) T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation.

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Related in: MedlinePlus

Flow cytometry analyses for the patterns of IFN-γ and/or IL-2                            production profile of total as well as the Tcm and Tem memory subsets of                                CD4+ T cells (A) and CD8+ T cells                            (B) in a representative animal from each of the three groups with                            different viral loads: Long-term non-progressors (LTNP), chronic viremia                            (Chronic), and highly viremic (Viremic).
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pone-0019607-g004: Flow cytometry analyses for the patterns of IFN-γ and/or IL-2 production profile of total as well as the Tcm and Tem memory subsets of CD4+ T cells (A) and CD8+ T cells (B) in a representative animal from each of the three groups with different viral loads: Long-term non-progressors (LTNP), chronic viremia (Chronic), and highly viremic (Viremic).

Mentions: It is believed that different subsets of CD4+ and CD8+ T cells play different functional roles with respect to antiviral immunity [6]. To test the functional characteristics of total CD4+ and CD8+ T cells as well as their memory subsets in the three groups of monkeys with different viral loads, we determined production of IL-2 and/or IFN-γ in response to in vitro stimulation with PMA+I by cytokine flow cytometry analysis, a technique that allows for precise quantification and phenotypic characterization of cytokine producing T cells [24], [25]. We observed substantial frequencies for the numbers of IFN-γ producing cells in the total as well as memory subsets of both CD4+ and CD8+ T cells, and these responses were restricted almost entirely to the population defined by memory phenotype as shown for a representative animal from each of the three groups studied (Figs. 4A and 4B). In general, we observed CD4+ as well as CD8+ T cells producing both IFN-γ and IL-2 after PMA+I stimulation in all three groups exhibiting different viral load levels, with the Tcm predominately producing IL-2 and the Tem producing IFN-γ. This is consistent with the effector function of Tem subset and the precursor function of Tcm subset to maintain the homeostasis of Tem during viral infections.


Functional impairment of central memory CD4 T cells is a potential early prognostic marker for changing viral load in SHIV-infected rhesus macaques.

He H, Nehete PN, Nehete B, Wieder E, Yang G, Buchl S, Sastry KJ - PLoS ONE (2011)

Flow cytometry analyses for the patterns of IFN-γ and/or IL-2                            production profile of total as well as the Tcm and Tem memory subsets of                                CD4+ T cells (A) and CD8+ T cells                            (B) in a representative animal from each of the three groups with                            different viral loads: Long-term non-progressors (LTNP), chronic viremia                            (Chronic), and highly viremic (Viremic).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3094340&req=5

pone-0019607-g004: Flow cytometry analyses for the patterns of IFN-γ and/or IL-2 production profile of total as well as the Tcm and Tem memory subsets of CD4+ T cells (A) and CD8+ T cells (B) in a representative animal from each of the three groups with different viral loads: Long-term non-progressors (LTNP), chronic viremia (Chronic), and highly viremic (Viremic).
Mentions: It is believed that different subsets of CD4+ and CD8+ T cells play different functional roles with respect to antiviral immunity [6]. To test the functional characteristics of total CD4+ and CD8+ T cells as well as their memory subsets in the three groups of monkeys with different viral loads, we determined production of IL-2 and/or IFN-γ in response to in vitro stimulation with PMA+I by cytokine flow cytometry analysis, a technique that allows for precise quantification and phenotypic characterization of cytokine producing T cells [24], [25]. We observed substantial frequencies for the numbers of IFN-γ producing cells in the total as well as memory subsets of both CD4+ and CD8+ T cells, and these responses were restricted almost entirely to the population defined by memory phenotype as shown for a representative animal from each of the three groups studied (Figs. 4A and 4B). In general, we observed CD4+ as well as CD8+ T cells producing both IFN-γ and IL-2 after PMA+I stimulation in all three groups exhibiting different viral load levels, with the Tcm predominately producing IL-2 and the Tem producing IFN-γ. This is consistent with the effector function of Tem subset and the precursor function of Tcm subset to maintain the homeostasis of Tem during viral infections.

Bottom Line: Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4(+) T cells, but not CD8(+) T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation.Highly viremic animals showed impaired cytokine-production by all T cells subsets.These results suggest that functional impairment of CD4(+) T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.

ABSTRACT
In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4(+) T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4(+) T cells, but not CD8(+) T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4(+) T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation.

Show MeSH
Related in: MedlinePlus