Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 γδ T lymphocytes

Lorenzo Dagna, Andrea Iellem, Priscilla Biswas, Davide Resta, Francesca Tantardini, Claudio Fortis, Maria Grazia Sabbadini, Daniele D'Ambrosio, Angelo A. Manfredi, Marina Ferrarini

Research output: Contribution to journalArticle

Abstract

Human Vγ9/Vδ2+ T lymphocytes participate in the immune response against intracellular pathogens through the secretion of type-1 cytokines and chemokines and by killing of infected cells. Little is known of the effects by type-2 differentiation of γδ cells on these functions. Here, we report that bona fide naive cord blood-derived γδ lymphocytes expanded in vitro with the mycobacterial antigen isopentenyl pyrophosphate (IPP) can be differentiated as either type-1 or type-2 cells, in the presence of an appropriate cytokine milieu. Instead, peripheral γδ cells from PPD-negative healthy adults displayed a type-1 cytokine profile, i.e. IPP-stimulated secretion of IFN-γ, but not of IL-4 and IL-10. Moreover, they released the macrophage inflammatory protein (MIP)-1β, but not IL-8 nor the Th2 chemoattractants I-309 and TARC (thymus and activation-regulated chemokine). This cytokine profile was not significantly affected by in vitro culture in Th2 polarizing conditions. Only in one case out of seven were peripheral γδ cells fully differentiated to type-2 lymphocytes, characterized by sustained IL-4 and IL-10 production, along with secretion of substantial amounts of IL-8, I-309 and TARC. Type-2 γδ T lymphocytes preferentially expressed the co-stimulatory molecule CD30; conversely, no skewing in chemokine receptor expression was observed. Both polarized populations displayed high levels of CXCR3 in the absence of CCR3, CCR4 and CCR5. Finally, type-1, but not type-2, γδ T lymphocytes killed IPP-pulsed U937 cells and displayed elevated perforin content. Overall, our data suggest that type-2 differentiation of γδ T lymphocytes profoundly affects both their effector functions and their potential to recruit the appropriate leukocyte subsets to the sites of inflammation.

Original languageEnglish
Pages (from-to)2934-2943
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 2002

Fingerprint

Chemokine Receptors
Chemokines
Chemokine CCL17
Cytokines
T-Lymphocytes
Interleukin-8
Interleukin-4
Interleukin-10
Lymphocytes
Macrophage Inflammatory Proteins
Perforin
U937 Cells
Tuberculin
Chemotactic Factors
Fetal Blood
Cell Differentiation
Leukocytes
Inflammation
Antigens
Population

Keywords

  • γδ lymphocyte
  • Chemokine
  • Cytokine
  • Th1/Th2 lymphocyte
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology

Cite this

Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 γδ T lymphocytes. / Dagna, Lorenzo; Iellem, Andrea; Biswas, Priscilla; Resta, Davide; Tantardini, Francesca; Fortis, Claudio; Sabbadini, Maria Grazia; D'Ambrosio, Daniele; Manfredi, Angelo A.; Ferrarini, Marina.

In: European Journal of Immunology, Vol. 32, No. 10, 10.2002, p. 2934-2943.

Research output: Contribution to journalArticle

Dagna, Lorenzo ; Iellem, Andrea ; Biswas, Priscilla ; Resta, Davide ; Tantardini, Francesca ; Fortis, Claudio ; Sabbadini, Maria Grazia ; D'Ambrosio, Daniele ; Manfredi, Angelo A. ; Ferrarini, Marina. / Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 γδ T lymphocytes. In: European Journal of Immunology. 2002 ; Vol. 32, No. 10. pp. 2934-2943.
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AU - Iellem, Andrea

AU - Biswas, Priscilla

AU - Resta, Davide

AU - Tantardini, Francesca

AU - Fortis, Claudio

AU - Sabbadini, Maria Grazia

AU - D'Ambrosio, Daniele

AU - Manfredi, Angelo A.

AU - Ferrarini, Marina

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N2 - Human Vγ9/Vδ2+ T lymphocytes participate in the immune response against intracellular pathogens through the secretion of type-1 cytokines and chemokines and by killing of infected cells. Little is known of the effects by type-2 differentiation of γδ cells on these functions. Here, we report that bona fide naive cord blood-derived γδ lymphocytes expanded in vitro with the mycobacterial antigen isopentenyl pyrophosphate (IPP) can be differentiated as either type-1 or type-2 cells, in the presence of an appropriate cytokine milieu. Instead, peripheral γδ cells from PPD-negative healthy adults displayed a type-1 cytokine profile, i.e. IPP-stimulated secretion of IFN-γ, but not of IL-4 and IL-10. Moreover, they released the macrophage inflammatory protein (MIP)-1β, but not IL-8 nor the Th2 chemoattractants I-309 and TARC (thymus and activation-regulated chemokine). This cytokine profile was not significantly affected by in vitro culture in Th2 polarizing conditions. Only in one case out of seven were peripheral γδ cells fully differentiated to type-2 lymphocytes, characterized by sustained IL-4 and IL-10 production, along with secretion of substantial amounts of IL-8, I-309 and TARC. Type-2 γδ T lymphocytes preferentially expressed the co-stimulatory molecule CD30; conversely, no skewing in chemokine receptor expression was observed. Both polarized populations displayed high levels of CXCR3 in the absence of CCR3, CCR4 and CCR5. Finally, type-1, but not type-2, γδ T lymphocytes killed IPP-pulsed U937 cells and displayed elevated perforin content. Overall, our data suggest that type-2 differentiation of γδ T lymphocytes profoundly affects both their effector functions and their potential to recruit the appropriate leukocyte subsets to the sites of inflammation.

AB - Human Vγ9/Vδ2+ T lymphocytes participate in the immune response against intracellular pathogens through the secretion of type-1 cytokines and chemokines and by killing of infected cells. Little is known of the effects by type-2 differentiation of γδ cells on these functions. Here, we report that bona fide naive cord blood-derived γδ lymphocytes expanded in vitro with the mycobacterial antigen isopentenyl pyrophosphate (IPP) can be differentiated as either type-1 or type-2 cells, in the presence of an appropriate cytokine milieu. Instead, peripheral γδ cells from PPD-negative healthy adults displayed a type-1 cytokine profile, i.e. IPP-stimulated secretion of IFN-γ, but not of IL-4 and IL-10. Moreover, they released the macrophage inflammatory protein (MIP)-1β, but not IL-8 nor the Th2 chemoattractants I-309 and TARC (thymus and activation-regulated chemokine). This cytokine profile was not significantly affected by in vitro culture in Th2 polarizing conditions. Only in one case out of seven were peripheral γδ cells fully differentiated to type-2 lymphocytes, characterized by sustained IL-4 and IL-10 production, along with secretion of substantial amounts of IL-8, I-309 and TARC. Type-2 γδ T lymphocytes preferentially expressed the co-stimulatory molecule CD30; conversely, no skewing in chemokine receptor expression was observed. Both polarized populations displayed high levels of CXCR3 in the absence of CCR3, CCR4 and CCR5. Finally, type-1, but not type-2, γδ T lymphocytes killed IPP-pulsed U937 cells and displayed elevated perforin content. Overall, our data suggest that type-2 differentiation of γδ T lymphocytes profoundly affects both their effector functions and their potential to recruit the appropriate leukocyte subsets to the sites of inflammation.

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