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Acyclovir Therapy Reduces the CD4+ T Cell Response against the Immunodominant pp65 Protein from Cytomegalovirus in Immune Competent Individuals.

Pachnio A, Begum J, Fox A, Moss P - PLoS ONE (2015)

Bottom Line: The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir.This effect was seen within one year of therapy and was observed primarily within the CD4+ response.These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

View Article: PubMed Central - PubMed

Affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

ABSTRACT
Cytomegalovirus (CMV) infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

No MeSH data available.


Related in: MedlinePlus

Frequency of pp65-specific T cells in patients taking acyclovir and in control subjects.IFN-γ production was determined in the total T cell population following stimulation with pp65 peptide pool using PBMC taken from ACV-treated subjects and control subjects (A). The individual responses of CD4+ T cells (B) and CD8+ T cells (C) are also shown. In (D-F) the proportion of pp65-specific T cells is represented accordingly in samples from donors who had been taking acyclovir for periods of 1–11 months, 12–48 months or over 4 years (n = 9, 8, 7 respectively). Means (A-C) or means with SEM (D-F) are shown.
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pone.0125287.g001: Frequency of pp65-specific T cells in patients taking acyclovir and in control subjects.IFN-γ production was determined in the total T cell population following stimulation with pp65 peptide pool using PBMC taken from ACV-treated subjects and control subjects (A). The individual responses of CD4+ T cells (B) and CD8+ T cells (C) are also shown. In (D-F) the proportion of pp65-specific T cells is represented accordingly in samples from donors who had been taking acyclovir for periods of 1–11 months, 12–48 months or over 4 years (n = 9, 8, 7 respectively). Means (A-C) or means with SEM (D-F) are shown.

Mentions: The magnitude of the overall T cell response to pp65 was 1.17% in the control group and this was reduced by 53% to a mean of 0.54% of the total T cell pool in donors receiving acyclovir (Fig 1A). This reduction was seen within the first year of treatment (Fig 1D). When looking in more detail it was observed, that the CD4+ T cell subset (Fig 1B) was more affected by the treatment than the CD8+ T cells (Fig 1C). In the control group on average 0.23% of CD4+ T cells were producing IFN-γ in response to pp65-derived peptides, whereas only 0.06% responded in the treated group (Fig 1B). Relating these results to the time on treatment we did not observe significant differences, although the IFN-γ response of CD4+ T cells was more reduced in patients who had taken the drug for at least 12 months (Fig 1E).


Acyclovir Therapy Reduces the CD4+ T Cell Response against the Immunodominant pp65 Protein from Cytomegalovirus in Immune Competent Individuals.

Pachnio A, Begum J, Fox A, Moss P - PLoS ONE (2015)

Frequency of pp65-specific T cells in patients taking acyclovir and in control subjects.IFN-γ production was determined in the total T cell population following stimulation with pp65 peptide pool using PBMC taken from ACV-treated subjects and control subjects (A). The individual responses of CD4+ T cells (B) and CD8+ T cells (C) are also shown. In (D-F) the proportion of pp65-specific T cells is represented accordingly in samples from donors who had been taking acyclovir for periods of 1–11 months, 12–48 months or over 4 years (n = 9, 8, 7 respectively). Means (A-C) or means with SEM (D-F) are shown.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4414608&req=5

pone.0125287.g001: Frequency of pp65-specific T cells in patients taking acyclovir and in control subjects.IFN-γ production was determined in the total T cell population following stimulation with pp65 peptide pool using PBMC taken from ACV-treated subjects and control subjects (A). The individual responses of CD4+ T cells (B) and CD8+ T cells (C) are also shown. In (D-F) the proportion of pp65-specific T cells is represented accordingly in samples from donors who had been taking acyclovir for periods of 1–11 months, 12–48 months or over 4 years (n = 9, 8, 7 respectively). Means (A-C) or means with SEM (D-F) are shown.
Mentions: The magnitude of the overall T cell response to pp65 was 1.17% in the control group and this was reduced by 53% to a mean of 0.54% of the total T cell pool in donors receiving acyclovir (Fig 1A). This reduction was seen within the first year of treatment (Fig 1D). When looking in more detail it was observed, that the CD4+ T cell subset (Fig 1B) was more affected by the treatment than the CD8+ T cells (Fig 1C). In the control group on average 0.23% of CD4+ T cells were producing IFN-γ in response to pp65-derived peptides, whereas only 0.06% responded in the treated group (Fig 1B). Relating these results to the time on treatment we did not observe significant differences, although the IFN-γ response of CD4+ T cells was more reduced in patients who had taken the drug for at least 12 months (Fig 1E).

Bottom Line: The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir.This effect was seen within one year of therapy and was observed primarily within the CD4+ response.These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

View Article: PubMed Central - PubMed

Affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

ABSTRACT
Cytomegalovirus (CMV) infects the majority of the global population and leads to the development of a strong virus-specific immune response. The CMV-specific CD4+ and CD8+ T cell immune response can comprise between 10 and 50% of the T cell pool within peripheral blood and there is concern that this may impair immunity to other pathogens. Elderly individuals with the highest magnitude of CMV-specific immune response have been demonstrated to be at increased risk of mortality and there is increasing interest in interventions that may serve to moderate this. Acyclovir is an anti-viral drug with activity against a range of herpes viruses and is used as long term treatment to suppress reactivation of herpes simplex virus. We studied the immune response to CMV in patients who were taking acyclovir to assess if therapy could be used to suppress the CMV-specific immune response. The T cell reactivity against the immunodominant late viral protein pp65 was reduced by 53% in people who were taking acyclovir. This effect was seen within one year of therapy and was observed primarily within the CD4+ response. Acyclovir treatment only modestly influenced the immune response to the IE-1 target protein. These data show that low dose acyclovir treatment has the potential to modulate components of the T cell response to CMV antigen proteins and indicate that anti-viral drugs should be further investigated as a means to reduce the magnitude of CMV-specific immune response and potentially improve overall immune function.

No MeSH data available.


Related in: MedlinePlus