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

• Published in: European journal of immunology 2002-10, Vol.32 (10), p.2934-2943
• Main Authors: Dagna, Lorenzo, Iellem, Andrea, Biswas, Priscilla, Resta, Davide, Tantardini, Francesca, Fortis, Claudio, Sabbadini, Maria Grazia, D'Ambrosio, Daniele, Manfredi, Angelo A., Ferrarini, Marina
• Format: Article
• Language: English
• Subjects: Cell Differentiation; Chemokine; Chemokines - biosynthesis; Cytokine; Cytotoxicity, Immunologic; Hemiterpenes; Humans; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Ki-1 Antigen - analysis; Membrane Glycoproteins - biosynthesis; Organophosphorus Compounds - immunology; Perforin; Pore Forming Cytotoxic Proteins; Receptors, Antigen, T-Cell, gamma-delta - analysis; Receptors, Chemokine - analysis; Th1 Cells - immunology; Th1/Th2 lymphocyte; Th2 Cells - immunology; Tuberculosis; U937 Cells; γ δ lymphocyte
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(2002010)32:10<2934::AID-IMMU2934>3.0.CO;2-6

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 γ δ cells on these functions. Here, we report that bona fide naive cord blood‐derived γ δ lymphocytesexpanded 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 γ δ 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 γ δ 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 γ δ 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, γ δ T lymphocytes killed IPP‐pulsed U937 cells and displayed elevated perforin content. Overall, our data suggest that type‐2 differentiation of γ δ T lymphocytes profoundly affects both their effector functions and their potential to recruit the appropriate leukocyte subsets to the sites of inflammation.