Trends in Immunology
γδ T cells: an alternative type of professional APC
Section snippets
The chemokine paradigm
Immune cells depend on stringent migration control mechanisms for carrying out their various immune functions. Leukocyte migration control is accomplished by a large array of chemokines, chemokine receptors and adhesion molecules 1, 2, 3, 4, 5. Chemokines target leukocytes expressing the corresponding chemokine receptors and regulate two crucial aspects in leukocyte relocation: (i) extravasation, in which endothelia-associated chemokines induce the firm attachment of circulating leukocytes to
Antigen presentation by activated Vδ2+ T cells
A large fraction of tonsillar γδ T cells are activated and express high levels of MHC II and the CD28 ligands CD80 and CD86, a fact that prompted a detailed analysis of APC functions in peripheral blood Vδ2+ T cells [24]. These studies were greatly facilitated by the broad responses in vitro of Vδ2+ T cells to IPP, one of several microbial agents responsible for the tremendous Vδ2+ T cell expansion seen during infections 17, 18, 19, 20, 21. APC features examined include (i) the expression of
A model for Vδ2+ T-APCs
What type of physiological circumstances could account for the generation of Vδ2+ T-APCs, and how would this novel type of APC become involved in adaptive immune processes? The model we propose here relies heavily on the functional duality in DCs that distinguishes between two states of maturation.
Peripheral blood Vδ2+ T cells are characterized by an inflammatory migration profile that guides them, together with innate leukocytes, to sites of infection where recently entered pathogens are in
Open questions
Our description of professional APC function in human Vδ2+ T cells might be highly relevant to immunotherapy (Box 1). This raises numerous questions, many of which relate to past and current activities within the field of DC research.
Acknowledgements
This work was supported by grant 31–106583 from the Swiss National Science Foundation and grant 03.0441–2 from the Staatssekretariat für Bildung und Forschung.
References (56)
- et al.
Chemokines and the tissue-specific migration of lymphocytes
Immunity
(2002) - et al.
Chemoattractants and their receptors in homeostasis and inflammation
Curr. Opin. Immunol.
(2004) Chemokines: multiple levels of leukocyte migration control
Trends Immunol.
(2004)CXCR5(+) T cells: follicular homing takes center stage in T-helper-cell responses
Trends Immunol.
(2002)Flexible migration program regulates γδ T-cell involvement in humoral immunity
Blood
(2003)Migration of Vδ1 and Vδ2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1-infected patients: competition by HIV-1 Tat
Blood
(2004)Activation of C-C β-chemokines in human peripheral blood γδ T cells by isopentenyl pyrophosphate and regulation by cytokines
Blood
(2000)- et al.
Adaptive immune response of Vγ2Vδ2 T cells: a new paradigm
Trends Immunol.
(2003) Microbial isoprenoid biosynthesis and human γδ T cell activation
FEBS Lett.
(2003)- et al.
The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics
Curr. Opin. Immunol.
(2001)
The cell biology of antigen presentation in dendritic cells
Curr. Opin. Immunol.
MICA engagement by human Vγ2Vδ2 T cells enhances their antigen-dependent effector function
Immunity
The use of dendritic cells in cancer immunotherapy
Curr. Opin. Immunol.
Distinct structure and signaling potential of the γδ TCR complex
Immunity
γδ T cells for immune therapy of patients with lymphoid malignancies
Blood
Induction of γδ T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo
Blood
Lymphocyte traffic control by chemokines
Nat. Immunol.
Homing and cellular traffic in lymph nodes
Nat. Rev. Immunol.
The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity
Immunol. Rev.
Central memory and effector memory T cell subsets: function, generation, and maintenance
Annu. Rev. Immunol.
Chemokines: control of primary and memory T-cell traffic
Immunol. Res.
Role of monocyte chemotactic protein-1/CC chemokine ligand 2 on γδ T lymphocyte trafficking during inflammation induced by lipopolysaccharide or Mycobacterium bovis bacille Calmette-Guerin
J. Immunol.
Patterns of chemokine receptor expression on peripheral blood γδ T lymphocytes: strong expression of CCR5 is a selective feature of Vδ2/Vγ9 γδ T cells
J. Immunol.
Differentiation of effector/memory Vδ2 T cells and migratory routes in lymph nodes or inflammatory sites
J. Exp. Med.
Transendothelial chemotaxis of human α/β and γ/δ T lymphocytes to chemokines
Eur. J. Immunol.
Intraepithelial lymphocytes: exploring the Third Way in immunology
Nat. Immunol.
γδ T cells: functional plasticity and heterogeneity
Nat. Rev. Immunol.
Antigen recognition by human γδ T cells: pattern recognition by the adaptive immune system
Springer Semin. Immunopathol.
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