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Gammadelta T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-alpha and IFN-gamma-producers in response to Pseudomonas aeruginosa.

Raga S, Julià MR, Crespí C, Figuerola J, Martínez N, Milà J, Matamoros N - Respir. Res. (2003)

Bottom Line: Gammadelta T cells have an important immunoregulatory and effector function through cytokine release.No differences were found between patients and controls.They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Immunology Service, Son Dureta Hospital, Palma de Mallorca, Balearic Islands, Spain. sraga305v@cv.gva.es <sraga305v@cv.gva.es>

ABSTRACT

Background: Gammadelta T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation.

Methods: The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-gamma and TNF-alpha production by gammadelta and alphabeta T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA). Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC) culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of gammadelta T cells were also evaluated.

Results: The highest production of cytokine was of TNF-alpha and IFN-gamma, gammadelta being better producers than alphabeta. No differences were found between patients and controls. The Vgamma9delta2 subset of gammadelta T cells was preferentially expanded. CD25 and CD45RO expression by the alphabeta T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes.

Conclusion: Our results support the hypothesis that gammadelta T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

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Percentage of CD45RO-expressing cells in αβ T lymphocytes (top) and γδ T lymphocytes (bottom), after 0, 4, 6, and 8 days of PBMC culture with cytosolic extract from Pseudomonas aeruginosa. Surface expression of CD45RO (memory/activation marker) was detected, by three color cytometry, in 2500 gated T lymphocytes from controls (n = 17), Cystic fibrosis patients infected by PA (CFp, n = 9) and Cystic fibrosis patients not infected by PA (CFn, n = 4). Bar values correspond to mean ± standard error of the mean. (top) αβ T lymphocytes: (*) significant difference between controls and CFp, (**) significant difference between controls and CFn (ANOVA, LSD PostHoc test). (bottom) γδ T lymphocytes: significant differences were not found between groups.
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Figure 3: Percentage of CD45RO-expressing cells in αβ T lymphocytes (top) and γδ T lymphocytes (bottom), after 0, 4, 6, and 8 days of PBMC culture with cytosolic extract from Pseudomonas aeruginosa. Surface expression of CD45RO (memory/activation marker) was detected, by three color cytometry, in 2500 gated T lymphocytes from controls (n = 17), Cystic fibrosis patients infected by PA (CFp, n = 9) and Cystic fibrosis patients not infected by PA (CFn, n = 4). Bar values correspond to mean ± standard error of the mean. (top) αβ T lymphocytes: (*) significant difference between controls and CFp, (**) significant difference between controls and CFn (ANOVA, LSD PostHoc test). (bottom) γδ T lymphocytes: significant differences were not found between groups.

Mentions: Before culture, the percentage of γδ CD45RO-positive cells was significantly higher in CFw (78.9 ± 3.2) than in controls (62.7 ± 5.6) (p < 0.05). When we separated patients into CFn and CFp groups, the difference was not significant (Fig 3). After day 4 there were no significant differences between CFw and controls, due to the increase in the control group. CD45RO expression was always significantly higher in γδ than in αβ, agreeing with other reports [33], in controls: p < 0.05 on day 0 and p < 0.001 during culture, in CFp: p < 0.001 on day 0 and during culture and in CFn: p < 0.05 on day 0 and during culture (Fig 3).


Gammadelta T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-alpha and IFN-gamma-producers in response to Pseudomonas aeruginosa.

Raga S, Julià MR, Crespí C, Figuerola J, Martínez N, Milà J, Matamoros N - Respir. Res. (2003)

Percentage of CD45RO-expressing cells in αβ T lymphocytes (top) and γδ T lymphocytes (bottom), after 0, 4, 6, and 8 days of PBMC culture with cytosolic extract from Pseudomonas aeruginosa. Surface expression of CD45RO (memory/activation marker) was detected, by three color cytometry, in 2500 gated T lymphocytes from controls (n = 17), Cystic fibrosis patients infected by PA (CFp, n = 9) and Cystic fibrosis patients not infected by PA (CFn, n = 4). Bar values correspond to mean ± standard error of the mean. (top) αβ T lymphocytes: (*) significant difference between controls and CFp, (**) significant difference between controls and CFn (ANOVA, LSD PostHoc test). (bottom) γδ T lymphocytes: significant differences were not found between groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC203157&req=5

Figure 3: Percentage of CD45RO-expressing cells in αβ T lymphocytes (top) and γδ T lymphocytes (bottom), after 0, 4, 6, and 8 days of PBMC culture with cytosolic extract from Pseudomonas aeruginosa. Surface expression of CD45RO (memory/activation marker) was detected, by three color cytometry, in 2500 gated T lymphocytes from controls (n = 17), Cystic fibrosis patients infected by PA (CFp, n = 9) and Cystic fibrosis patients not infected by PA (CFn, n = 4). Bar values correspond to mean ± standard error of the mean. (top) αβ T lymphocytes: (*) significant difference between controls and CFp, (**) significant difference between controls and CFn (ANOVA, LSD PostHoc test). (bottom) γδ T lymphocytes: significant differences were not found between groups.
Mentions: Before culture, the percentage of γδ CD45RO-positive cells was significantly higher in CFw (78.9 ± 3.2) than in controls (62.7 ± 5.6) (p < 0.05). When we separated patients into CFn and CFp groups, the difference was not significant (Fig 3). After day 4 there were no significant differences between CFw and controls, due to the increase in the control group. CD45RO expression was always significantly higher in γδ than in αβ, agreeing with other reports [33], in controls: p < 0.05 on day 0 and p < 0.001 during culture, in CFp: p < 0.001 on day 0 and during culture and in CFn: p < 0.05 on day 0 and during culture (Fig 3).

Bottom Line: Gammadelta T cells have an important immunoregulatory and effector function through cytokine release.No differences were found between patients and controls.They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Immunology Service, Son Dureta Hospital, Palma de Mallorca, Balearic Islands, Spain. sraga305v@cv.gva.es <sraga305v@cv.gva.es>

ABSTRACT

Background: Gammadelta T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation.

Methods: The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-gamma and TNF-alpha production by gammadelta and alphabeta T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA). Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC) culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of gammadelta T cells were also evaluated.

Results: The highest production of cytokine was of TNF-alpha and IFN-gamma, gammadelta being better producers than alphabeta. No differences were found between patients and controls. The Vgamma9delta2 subset of gammadelta T cells was preferentially expanded. CD25 and CD45RO expression by the alphabeta T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes.

Conclusion: Our results support the hypothesis that gammadelta T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

Show MeSH
Related in: MedlinePlus