Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vγ9/Vδ2 T cells in tumor immunity

Fisch, Paul; Meuer, Eva; Pende, Daniela; Rothenfußer, Simon; Viale, Oriane; Kock, Sylvia; Ferrone, Soldano; Fradelizi, D; Klein, George; Moretta, Lorenzo; Rammensee, Hans Georg; Boon, Thierry; Coulie, Pierre G.; Bruggen, Pierre van der

doi:10.1002/eji.1830271236

Cited by 112 publications

(84 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Natural killer (NK) cells share some characteristics with cd T cells as both are usually considered constituents of innate immunity, recognize transformed cells, play a prominent role in antiviral protection and are cytolytic lymphocytes. [8][9][10] Like NK cells, human cd T cells express activating receptors, such as NKG2D that recognizes stress-inducible MHC class I-related MICA/MICB molecules and the UL16-binding proteins that are upregulated on malignant or stressed cells and induce cytolysis, 11,12 and they are inhibited by the expression of killer Ig-like receptors, which bind certain MHC class I alleles expressed by nonmalignant cells and trophoblasts. [13][14][15] However, the versatility of cd T cells is further extended by their demonstrated ability to assume the role and appearance of professional antigen presenting cells.…”

Section: Prologuementioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

View full text Add to dashboard Cite

The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

show abstract

Section: Prologuementioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

View full text Add to dashboard Cite

show abstract

“…Mature Vg9Vd2 cells sampled from blood or expanded in vitro also recognize diverse tumor cell types against which they frequently exert cytotoxicity. This cytolytic activity is regulated by activatory and inhibitory receptors for classical and nonclassical MHC class I (MHC-I) Ags (NKG2D and NKRs) (3,4) and molecular pattern recognition receptors, such as TLRs, although activation through their TCR is essential (5,6). The Vg9Vd2 TCR is thought to function as a pathogen-associated molecular pattern receptor dedicated to the recognition of small pyrophosphorylated alkyls.…”

mentioning

confidence: 99%

F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells

Mookerjee‐Basu

Vantourout

Martinez

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…So, the intracellular dominance of signaling from gd TCR versus TGF-bR determines the outcome of functional gd cell responses to their microenvironment, like the gd TCR versus KIR relationship (78)(79)(80). Because increasing doses of stimulating PAg/ IL-2 can overcome the inhibition of cytolytic TCRVg9 + T cells by TGF-b, strategies bypassing its bioactivity could be envisaged.…”

Section: Discussionmentioning

confidence: 99%

Phosphoantigens Overcome Human TCRVγ9+ γδ Cell Immunosuppression by TGF-β: Relevance for Cancer Immunotherapy

Capietto

Martinet

Cendron

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Human γδ cells expressing TCRVγ9 are HLA-unrestricted CTLs with high relevance for cancer immunotherapy. Many tumor cell types produce TGF-β, however, a cytokine strongly immunosuppressive for conventional T CD4, CD8, and NK cells. Whether TGF-β also inhibits TCRVγ9+ lymphocytes was unknown. Because phosphoantigens (PAgs), such as bromohydrin pyrophosphate, selectively activate the antitumor functions of TCRVγ9+ T cells, in this study, we investigated whether TGF-β modulates these functions. We report that TGF-β does not block activation of TCRVγ9+ T cells but inhibits their PAg/IL-2–induced proliferation and maturation into effector cells and finally reduces the cytotoxic activity of these γδ T cells when exposed to lymphoma target cells. TGF-β did not bias their differentiation pattern toward γδ Th17 or γδ regulatory T cells. Nevertheless, increasing doses of PAg stimulus countered TGF-β inhibition. So, although TGF-β impairs TCRVγ9+ γδ cells like other cytolytic lymphocytes, PAg alone or combined to therapeutic mAb has the ability to bypass its immunosuppressive activity.

show abstract

Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vγ9/Vδ2 T cells in tumor immunity

Cited by 112 publications

References 50 publications

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells

Phosphoantigens Overcome Human TCRVγ9+ γδ Cell Immunosuppression by TGF-β: Relevance for Cancer Immunotherapy

Contact Info

Product

Resources

About