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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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Flow cytometry analyses showing the distribution of total                                CD3+ T cells along with subsets CD4+                                CD8− (CD4+ T cells) and                                CD4− CD8+ (CD8+ T                            cells).Panel A: data from a representative animal from each of the three groups                            of macaques with different viral loads: Long-term non-progressors                            (LTNP), chronic viremia (Chronic), and highly viremic (Viremic). Panel                            B: comparison of the average values for the numbers of total                                CD3+ T cells as well as CD4+                                CD8− and CD4− CD8+                            T cells subsets in all the animals studied in the LTNP, Chronic and                            Viremic groups of monkeys. The data are shown as the mean ± SEM.                            The Horizontal bars represent the group mean, error bars represent SEM.                            Statistical differences between groups are indicated by the                                p values.
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pone-0019607-g002: Flow cytometry analyses showing the distribution of total CD3+ T cells along with subsets CD4+ CD8− (CD4+ T cells) and CD4− CD8+ (CD8+ T cells).Panel A: data from a representative animal from each of the three groups of macaques with different viral loads: Long-term non-progressors (LTNP), chronic viremia (Chronic), and highly viremic (Viremic). Panel B: comparison of the average values for the numbers of total CD3+ T cells as well as CD4+ CD8− and CD4− CD8+ T cells subsets in all the animals studied in the LTNP, Chronic and Viremic groups of monkeys. The data are shown as the mean ± SEM. The Horizontal bars represent the group mean, error bars represent SEM. Statistical differences between groups are indicated by the p values.

Mentions: The CD4+ T cells play an important role in maintaining effective immunity against viral pathogens, specifically by providing help to B cells for antiviral antibody production and to cytotoxic T lymphocytes (CTL) for eliminating virus-infected cells [17], [18]. We first examined the numbers of total CD3+ T cells as well as CD4+ and CD8+ T cells subsets in all the animals tested and representative data from one animal each in the three different groups (Fig. 2A). As described in the methods section, in order to perform uniform analyses across the three groups of animals as defined by viral loads, we normalized the data for the phenotypic and functional properties of the different subsets of T cells to an arbitrary total number of 10,000 input peripheral blood lymphocytes (PBL). Based on this criterion we observed that the number of total CD3+ T cells in the LTNP group (6676±254; Mean ± SEM) were significantly higher (p = 0.0123) compared to that in the Chronic group (5493±362) and also the Viremic group (5559±555; p = 0.0441), but no differences were noted between the Chronic and the Viremic groups (Fig. 2B). With regards to the CD4+ T cells, the mean number in the LTNP (3709±255) was significantly higher (p<0.0001) than that in the Chronic group (1362±163) and the Viremic group (464±96; p = 0.0002), as well as between the LTNP and the Viremic groups (p<0.0001). These results obtained using the arbitrarily selected total number of 10,000 PBL for the analyses are consistent with literature norms showing that both the Chronic and Viremic groups of monkeys with medium to higher viral loads exhibited significantly lower numbers of CD4+ T cells. The number of CD8+ T cells exhibited a reverse trend with the LTNP group (2901±145) significantly lower (p<0.0001) than the Viremic group (5042±519) and also the Chronic group (4081±459; p = 0.0043), but no differences were observed between the Chronic and the Viremic groups.


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 showing the distribution of total                                CD3+ T cells along with subsets CD4+                                CD8− (CD4+ T cells) and                                CD4− CD8+ (CD8+ T                            cells).Panel A: data from a representative animal from each of the three groups                            of macaques with different viral loads: Long-term non-progressors                            (LTNP), chronic viremia (Chronic), and highly viremic (Viremic). Panel                            B: comparison of the average values for the numbers of total                                CD3+ T cells as well as CD4+                                CD8− and CD4− CD8+                            T cells subsets in all the animals studied in the LTNP, Chronic and                            Viremic groups of monkeys. The data are shown as the mean ± SEM.                            The Horizontal bars represent the group mean, error bars represent SEM.                            Statistical differences between groups are indicated by the                                p values.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3094340&req=5

pone-0019607-g002: Flow cytometry analyses showing the distribution of total CD3+ T cells along with subsets CD4+ CD8− (CD4+ T cells) and CD4− CD8+ (CD8+ T cells).Panel A: data from a representative animal from each of the three groups of macaques with different viral loads: Long-term non-progressors (LTNP), chronic viremia (Chronic), and highly viremic (Viremic). Panel B: comparison of the average values for the numbers of total CD3+ T cells as well as CD4+ CD8− and CD4− CD8+ T cells subsets in all the animals studied in the LTNP, Chronic and Viremic groups of monkeys. The data are shown as the mean ± SEM. The Horizontal bars represent the group mean, error bars represent SEM. Statistical differences between groups are indicated by the p values.
Mentions: The CD4+ T cells play an important role in maintaining effective immunity against viral pathogens, specifically by providing help to B cells for antiviral antibody production and to cytotoxic T lymphocytes (CTL) for eliminating virus-infected cells [17], [18]. We first examined the numbers of total CD3+ T cells as well as CD4+ and CD8+ T cells subsets in all the animals tested and representative data from one animal each in the three different groups (Fig. 2A). As described in the methods section, in order to perform uniform analyses across the three groups of animals as defined by viral loads, we normalized the data for the phenotypic and functional properties of the different subsets of T cells to an arbitrary total number of 10,000 input peripheral blood lymphocytes (PBL). Based on this criterion we observed that the number of total CD3+ T cells in the LTNP group (6676±254; Mean ± SEM) were significantly higher (p = 0.0123) compared to that in the Chronic group (5493±362) and also the Viremic group (5559±555; p = 0.0441), but no differences were noted between the Chronic and the Viremic groups (Fig. 2B). With regards to the CD4+ T cells, the mean number in the LTNP (3709±255) was significantly higher (p<0.0001) than that in the Chronic group (1362±163) and the Viremic group (464±96; p = 0.0002), as well as between the LTNP and the Viremic groups (p<0.0001). These results obtained using the arbitrarily selected total number of 10,000 PBL for the analyses are consistent with literature norms showing that both the Chronic and Viremic groups of monkeys with medium to higher viral loads exhibited significantly lower numbers of CD4+ T cells. The number of CD8+ T cells exhibited a reverse trend with the LTNP group (2901±145) significantly lower (p<0.0001) than the Viremic group (5042±519) and also the Chronic group (4081±459; p = 0.0043), but no differences were observed between the Chronic and the Viremic groups.

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