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Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus.

Willberg CB, McConnell JJ, Eriksson EM, Bragg LA, York VA, Liegler TJ, Hecht FM, Grant RM, Nixon DF - PLoS Pathog. (2008)

Bottom Line: Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners.Responses consisted of both CD4(+) and CD8(+) T cell subsets.However, no evidence for systemic super-infection was found in any of the individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA. Chris.Willberg@ndm.ox.ac.uk

ABSTRACT
Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-gamma enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4(+) and CD8(+) T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure.

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Related in: MedlinePlus

Exposure did not increase poly-functionality.The ability of CD8+ (A) and CD4+ (B) T cells to express IFN-γ and IL-2 was assessed in both the VP group (shaded boxes, n = 5) and NVP group (open boxes, n = 8). Poly-functionality was determined by the expression of both cytokines. Only the percentage of IL-2 expressing CD8+ T cells was significantly higher in the VP group (p = 0.0059), denoted by *.
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ppat-1000185-g005: Exposure did not increase poly-functionality.The ability of CD8+ (A) and CD4+ (B) T cells to express IFN-γ and IL-2 was assessed in both the VP group (shaded boxes, n = 5) and NVP group (open boxes, n = 8). Poly-functionality was determined by the expression of both cytokines. Only the percentage of IL-2 expressing CD8+ T cells was significantly higher in the VP group (p = 0.0059), denoted by *.

Mentions: In recent studies poly-functional T cells have been associated with slower disease progression [12]. PBMC from 8 individuals from the viremic partner group and 10 from the individuals from the non-viremic partner group were stimulated with 15mer peptide pools covering HIV-1 Gag and RT. CD4+ and CD8+ T cell expression of IFN-γ and IL-2 were measured by multi-parametric flow cytometry (Figure 5). No significant difference in the level of poly-functionality was seen between the two groups, although there was a trend for greater responses in the viremic partner group. IL-2 expression by CD8+ T cells was significantly higher (p = 0.0059) in the viremic partner group compared to the non-viremic partner group. In the positive control, SEB stimulation, revealed poly-functional T cells (data not shown).


Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus.

Willberg CB, McConnell JJ, Eriksson EM, Bragg LA, York VA, Liegler TJ, Hecht FM, Grant RM, Nixon DF - PLoS Pathog. (2008)

Exposure did not increase poly-functionality.The ability of CD8+ (A) and CD4+ (B) T cells to express IFN-γ and IL-2 was assessed in both the VP group (shaded boxes, n = 5) and NVP group (open boxes, n = 8). Poly-functionality was determined by the expression of both cytokines. Only the percentage of IL-2 expressing CD8+ T cells was significantly higher in the VP group (p = 0.0059), denoted by *.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2562513&req=5

ppat-1000185-g005: Exposure did not increase poly-functionality.The ability of CD8+ (A) and CD4+ (B) T cells to express IFN-γ and IL-2 was assessed in both the VP group (shaded boxes, n = 5) and NVP group (open boxes, n = 8). Poly-functionality was determined by the expression of both cytokines. Only the percentage of IL-2 expressing CD8+ T cells was significantly higher in the VP group (p = 0.0059), denoted by *.
Mentions: In recent studies poly-functional T cells have been associated with slower disease progression [12]. PBMC from 8 individuals from the viremic partner group and 10 from the individuals from the non-viremic partner group were stimulated with 15mer peptide pools covering HIV-1 Gag and RT. CD4+ and CD8+ T cell expression of IFN-γ and IL-2 were measured by multi-parametric flow cytometry (Figure 5). No significant difference in the level of poly-functionality was seen between the two groups, although there was a trend for greater responses in the viremic partner group. IL-2 expression by CD8+ T cells was significantly higher (p = 0.0059) in the viremic partner group compared to the non-viremic partner group. In the positive control, SEB stimulation, revealed poly-functional T cells (data not shown).

Bottom Line: Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners.Responses consisted of both CD4(+) and CD8(+) T cell subsets.However, no evidence for systemic super-infection was found in any of the individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA. Chris.Willberg@ndm.ox.ac.uk

ABSTRACT
Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-gamma enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4(+) and CD8(+) T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure.

Show MeSH
Related in: MedlinePlus