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Granzyme B mediated function of Parvovirus B19-specific CD4(+) T cells.

Kumar A, Perdomo MF, Kantele A, Hedman L, Hedman K, Franssila R - Clin Transl Immunology (2015)

Bottom Line: CD4(+) T cells with strong GrB responses were found to exhibit direct cytotoxicity.Our results suggest a role for CD4(+) CTL in B19 immunity.Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Haartman Institute, University of Helsinki , Helsinki, Finland.

ABSTRACT
A novel conception of CD4(+) T cells with cytolytic potential (CD4(+) CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4(+) CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4(+) T cells. CD4(+) T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4(+) T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4(+) CTLs co-expressing CD56 antigen. Our results suggest a role for CD4(+) CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.

No MeSH data available.


Related in: MedlinePlus

Correlation analysis. (a, b) Correlation between B19-specific IFN-γ and GrB responses among B19-seropositive (a) and -seronegative (b) individuals. (c, d) HBoV1 versus B19-specific GrB responses among the B19-seropositive (c) and -seronegative (d) subjects. Antigen concentrations were 1.5 μg ml−1. Spearman's correlation test was used.
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fig1: Correlation analysis. (a, b) Correlation between B19-specific IFN-γ and GrB responses among B19-seropositive (a) and -seronegative (b) individuals. (c, d) HBoV1 versus B19-specific GrB responses among the B19-seropositive (c) and -seronegative (d) subjects. Antigen concentrations were 1.5 μg ml−1. Spearman's correlation test was used.

Mentions: First, correlations between the B19-specific interferon gamma (IFN-γ) and GrB responses were studied among the 30 B19-seropositive and 22 seronegative subjects. As shown in Figure 1a, a strong correlation (P<0.0001) was found between the IFN-γ and GrB in the B19-seropositive group, whereas the respective correlation was less significant (P=0.024) among the seronegative subjects (Figure 1b). No significant correlation (P=0.53) was found between HBoV1- and B19-specific GrB responses among the B19-seropositive subject (Figure 1c). Most of the B19-seronegative subjects showed virtually absent B19-specific GrB response (Figure 1c).


Granzyme B mediated function of Parvovirus B19-specific CD4(+) T cells.

Kumar A, Perdomo MF, Kantele A, Hedman L, Hedman K, Franssila R - Clin Transl Immunology (2015)

Correlation analysis. (a, b) Correlation between B19-specific IFN-γ and GrB responses among B19-seropositive (a) and -seronegative (b) individuals. (c, d) HBoV1 versus B19-specific GrB responses among the B19-seropositive (c) and -seronegative (d) subjects. Antigen concentrations were 1.5 μg ml−1. Spearman's correlation test was used.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524951&req=5

fig1: Correlation analysis. (a, b) Correlation between B19-specific IFN-γ and GrB responses among B19-seropositive (a) and -seronegative (b) individuals. (c, d) HBoV1 versus B19-specific GrB responses among the B19-seropositive (c) and -seronegative (d) subjects. Antigen concentrations were 1.5 μg ml−1. Spearman's correlation test was used.
Mentions: First, correlations between the B19-specific interferon gamma (IFN-γ) and GrB responses were studied among the 30 B19-seropositive and 22 seronegative subjects. As shown in Figure 1a, a strong correlation (P<0.0001) was found between the IFN-γ and GrB in the B19-seropositive group, whereas the respective correlation was less significant (P=0.024) among the seronegative subjects (Figure 1b). No significant correlation (P=0.53) was found between HBoV1- and B19-specific GrB responses among the B19-seropositive subject (Figure 1c). Most of the B19-seronegative subjects showed virtually absent B19-specific GrB response (Figure 1c).

Bottom Line: CD4(+) T cells with strong GrB responses were found to exhibit direct cytotoxicity.Our results suggest a role for CD4(+) CTL in B19 immunity.Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Haartman Institute, University of Helsinki , Helsinki, Finland.

ABSTRACT
A novel conception of CD4(+) T cells with cytolytic potential (CD4(+) CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4(+) CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4(+) T cells. CD4(+) T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4(+) T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4(+) CTLs co-expressing CD56 antigen. Our results suggest a role for CD4(+) CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.

No MeSH data available.


Related in: MedlinePlus