CXCR5 identifies a subset of Vgamma9Vdelta2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production.

Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.
The Journal of Immunology (Impact Factor: 5.36). 11/2006; 177(8):5290-5. DOI: 10.4049/jimmunol.177.8.5290
Source: PubMed

ABSTRACT Vgamma9Vdelta2 T lymphocytes recognize nonpeptidic Ags and mount effector functions in cellular immune responses against microorganisms and tumors, but little is known about their role in Ab-mediated immune responses. We show here that expression of CXCR5 identifies a unique subset of Vgamma9Vdelta2 T cells which express the costimulatory molecules ICOS and CD40L, secrete IL-2, IL-4, and IL-10 and help B cells for Ab production. These properties portray CXCR5+ Vgamma9Vdelta2 T cells as a distinct memory T cell subset with B cell helper function.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Unconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vγ9/Vδ2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vγ9/Vδ2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines. Copyright © 2015. Published by Elsevier Inc.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The broad and potent tumor-reactivity of innate-like γδT cells makes them valuable additions to current cancer immunotherapeutic concepts based on adaptive immunity, such as monoclonal antibodies and αβT cells. However, clinical success using γδT cells to treat cancer has so far fallen short. Efforts of recent years have revealed a striking diversity in γδT cell functions and immunobiology, putting these cells forward as true "swiss army knives" of immunity. At the same time, however, this heterogeneity poses new challenges to the design of γδT cell-based therapeutic concepts and could explain their rather limited clinical efficacy in cancer patients. This review outlines the recent new insights into the different levels of γδT cell diversity, including the myriad of γδT cell-mediated immune functions, the diversity of specificities and affinities within the γδT cell repertoire, and the multitude of complex molecular requirements for γδT cell activation. A careful consideration of the diversity of antibodies and αβT cells has delivered great progress to their clinical success; addressing also the extraordinary diversity in γδT cells will therefore hold the key to more effective immunotherapeutic strategies with γδT cells as additional and valuable tools to battle cancer.
    Frontiers in Immunology 01/2014; 5:601. DOI:10.3389/fimmu.2014.00601
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human γδ T cells expressing the Vγ9Vδ2 T cell receptor can induce maturation of dendritic cells (DC) into antigen-presenting cells (APC) and B cells into antibody-secreting plasma cells. Since B cells are capable of presenting antigens to T cells, we investigated if Vγ9Vδ2 T cells can influence antigen-presentation by these cells. We report that Vγ9Vδ2 T cells induced expression of CD86, HLA-DR, and CD40 by B cells and stimulated the release of IL-4, IL-6, TNF-α, and IgG, IgA, and IgM. Vγ9Vδ2 T cells also augmented the ability of B cells to stimulate proliferation but not IFN-γ or IL-4 release by alloreactive T cells. In contrast, Vγ9Vδ2 T cells induced expression of CD86 and HLA-DR and the release of IFN-γ, IL-6, and TNF-α by DC and these DC stimulated proliferation and IFN-γ production by conventional T cells. Furthermore, CD86, TNF-α, IFN-γ, and cell contact were found to be important in DC activation by Vγ9Vδ2 T cells but not in the activation of B cells. These data suggest that Vγ9Vδ2 T cells can induce maturation of B cells and DC into APC, but while they prime DC to stimulate T helper 1 (TH1) responses, they drive maturation of B cells into APC that can stimulate different T cell responses. Thus, Vγ9Vδ2 T cells can control different arms of the immune system through selective activation of B cells and DC in vitro, which may have important applications in immunotherapy and for vaccine adjuvants.
    Frontiers in Immunology 12/2014; 5. DOI:10.3389/fimmu.2014.00650

Full-text (2 Sources)

Available from
May 19, 2014