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


CONCLUSIONS
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.
Raga
Salvador
S
Immunology Service, Son Dureta Hospital, Palma de Mallorca, Balearic Islands, Spain. sraga305v@cv.gva.es <sraga305v@cv.gva.es>
Julià
M Rosa
MR
Crespí
Catalina
C
Figuerola
Joan
J
Martínez
Natalia
N
Milà
Joan
J
Matamoros
Núria
N
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007425:Intracellular Membranes / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D009000:Monocytes / Q000473:pathology; D010641:Phenotype; D011552:Pseudomonas Infections / Q000150:complications*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate