scholarly journals Expansion of Human Peripheral Blood γδ T Cells using Zoledronate

10.3791/3182 ◽  
2011 ◽  
Author(s):  
Makoto Kondo ◽  
Takamichi Izumi ◽  
Nao Fujieda ◽  
Atsushi Kondo ◽  
Takeharu Morishita ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Gamma Delta T Cells ◽  
Gamma Delta

scholarly journals Constitutive expression of pore-forming protein in peripheral blood gamma/delta T cells: implication for their cytotoxic role in vivo.

1990 ◽  
Vol 172 (6) ◽  
pp. 1877-1880 ◽  
Author(s):  
M Nakata ◽  
M J Smyth ◽  
Y Norihisa ◽  
A Kawasaki ◽  
Y Shinkai ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic Activity ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Constitutive Expression ◽  
Immunocytochemical Staining ◽  
Target Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta

The cytotoxic activity and pore-forming protein (PFP) expression of human peripheral blood (PB) gamma/delta T cells were examined. Fresh gamma/delta T cells isolated from PB lymphocytes by fluorescence-activated cell sorting exhibited a substantial natural killer-like cytotoxic activity against K562 target cells and had a high cytotoxic potential triggered by anti-CD3 monoclonal antibody (mAb) against P815 target cells bearing Fc gamma R. Immunocytochemical staining with an anti-PFP mAb revealed that virtually all PB gamma/delta T cells are granular lymphocytes with abundant PFP in their cytoplasmic granules. Constitutive expression of PFP in PB gamma/delta T cells was also demonstrated by Northern blot analysis. These observations support the proposed role of gamma/delta T cells in cytolytic immune surveillance in vivo.

scholarly journals A large fraction of human peripheral blood gamma/delta + T cells is activated by Mycobacterium tuberculosis but not by its 65-kD heat shock protein.

1990 ◽  
Vol 171 (3) ◽  
pp. 667-679 ◽  
Author(s):  
D Kabelitz ◽  
A Bender ◽  
S Schondelmaier ◽  
B Schoel ◽  
S H Kaufmann
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Mhc Class Ii ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Large Fraction ◽  
Gamma Delta T Cells ◽  
Feeder Cells ◽  
Gamma Delta

We report that M. tuberculosis organisms, but neither PHA nor allogeneic stimulator cells, preferentially activate gamma/delta+ cells within E rosette-purified peripheral blood T cells. gamma/delta+ T cells from purified protein derivative (PPD)-nonimmune healthy donors were enriched by depletion of CD4+ and CD8+ cells; double-negative (DN) cells contained 65-92% gamma/delta+ T cells. Limiting dilution (LD) analyses revealed that 1 of 2-19 purified DN cells proliferated in response to mycobacteria, while frequencies of DN cells proliferating in response to a recombinant 65-kD heat shock protein (hsp 65) of M. tuberculosis/M. bovis were 10-20-fold lower. Established clones of mycobacteria-reactive gamma/delta+ T cells specifically recognized mycobacteria, but neither PPD nor hsp 65. Restimulation of these clones required the presence of PBMC feeder cells; EBV-transformed lymphoblastoid cell lines could not substitute for PBMC. Mycobacteria-reactive gamma/delta+ clones proliferated equally well in the presence of autologous or allogeneic (HLA-DR-different) PBMC feeder cells and thus were not MHC class II restricted. Taken together, these results demonstrate that mycobacteria-reactive gamma/delta+ T cells are present in high frequency in the peripheral blood of healthy individuals, and suggest that hsp 65 of mycobacteria is not a major antigen for gamma/delta+ T cells of normal PPD-nonimmune blood donors.

scholarly journals Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

1994 ◽  
Vol 179 (1) ◽  
pp. 311-315 ◽  
Author(s):  
M K Perera ◽  
R Carter ◽  
R Goonewardene ◽  
K N Mendis
Keyword(s):  
T Cells ◽  
Plasmodium Vivax ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Gastrointestinal Symptoms ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Endemic Region ◽  
Gastrointestinal Pathology

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p < 0.005 and < 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted < or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p < 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.

Dendritic Cells Can Be Primed to Concurrently Activate Both Unconventional Gamma/delta and Conventional alpha/beta T Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3893-3893
Author(s):  
Francesca Fiore ◽  
Barbara Castella ◽  
Barbara Nuschak ◽  
Raffaello Bertieri ◽  
Sara Mariani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Adoptive Cell Therapy ◽  
Effector Memory ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta

Abstract Vgamma9/Vdelta2 (gamma/delta) T cells represent the major subset of unconventional T cells circulating in the peripheral blood. Gamma/delta T cells play a major role in immune defenses against microbes, stressed cells and tumor cells. This property is based on their capability to naturally recognize phosphoantigens (pAgs), which are produced via the mevalonate (Mev) or the DOXP pathway in mammalian and nonmammalian cells, and induced self-ligands, which are de novo expressed or upregulated on the surface of stressed or tumor cells. Interestingly, gamma/delta T cells can also be activated by aminobisphosphonates (ABP)-treated monocytes. We have previously shown that ABP specifically target the Mev pathway of monocytes and induce the accumulation of phosphorylated Mev metabolites naturally recognized by gamma/delta T cells. The aim of this work was to determine whether ABP-treated dendritic cells (DC) can also activate gamma/delta T cells and whether this activation, if any, is detrimental or beneficial to the generation of antigen (Ag)-specific MHC-restricted immune responses mediated by conventional alpha/beta T cells. To this end, we have generated highly purified immature (iDC) and mature DC (mDC) from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol is the most potent ABP currently available for clinical use. Zol treatment did not affect the phenotype and immunostimulatory properties of iDC and mDC. Zol-treated iDC and mDC induced a rapid and vigorous expansion of central memory and effector memory gamma/delta T cells. Zol-treated iDC were more potent inducers of gamma/delta T-cell activation than mDC and monocytes. Activated gamma/delta T cells displayed antitumor activity and expressed on the cell surface the appropriate antigen repertoire to target secondary lymphoid organs and exert costimulatory activity on conventional alpha/beta T cells. Indeed, an in vitro model showed that antigen-specific MHC-restricted immune responses againt the influenza matrix peptide were significantly improved by the concurrent activation of gamma/delta T cells. This is the first report showing that: 1) DC can simultaneously be primed to activate both gamma/delta and alpha/beta T cells; 2) the former act as cellular adjuvants for the development of adaptive immune responses. In conclusion, large numbers of gamma/delta T cells with effector and costimulatory activities can rapidly be generated by Zol-treated iDC/mDC. This strategy is worth of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.

Gamma-delta T cells in the peripheral blood of rheumatoid arthritis patients — Correlation with the activity of the disease

1997 ◽  
Vol 56 ◽  
pp. 313
Author(s):  
O. Kowal-Bielecka ◽  
K. Bernacka ◽  
A. Kuryliszyn-Moskal ◽  
R. Mróz ◽  
E. Kowal
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Peripheral Blood ◽  
Gamma Delta T Cells ◽  
Gamma Delta

scholarly journals Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire.

1990 ◽  
Vol 171 (5) ◽  
pp. 1597-1612 ◽  
Author(s):  
C M Parker ◽  
V Groh ◽  
H Band ◽  
S A Porcelli ◽  
C Morita ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Gene Segment ◽  
Lymphoid Tissues ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Age Related ◽  
Gene Usage ◽  
V Gene ◽  
Age Related Changes

The germline repertoire of variable genes for the TCR-gamma/delta is limited. This, together with the availability of several V delta-specific and a C delta-specific mAbs, has made it possible to assess differences in the TCR-gamma/delta repertoire in man. TCR-gamma/delta cells expressing particular V gene segments have been previously shown to be localized in different anatomical sites. In this study, analysis of TCR-gamma/delta V gene segment usage performed on subjects from the time of birth through adulthood revealed striking age-related changes in the TCR-gamma/delta repertoire in peripheral blood. V delta 1+ gamma/delta T cells predominated in thymus as well as in peripheral blood at birth and then persisted as a relatively constant proportion of CD3+ PBL. However, V delta 2+ gamma/delta T cells that constitute a small proportion of the CD3+ cells in thymus and in peripheral blood at birth, then expand and account for the major population of gamma/delta T cells in PBL in adults. No parallel postnatal expansion of V delta 2+ cells in the thymus was observed, even when paired thymus-peripheral blood specimens were obtained on subjects between the ages of 3 d and 8 yr. The subset of V delta 2+ lymphocytes that was expanded in peripheral blood expressed high levels of CD45RO suggesting prior activation of these cells, consistent with the possibility that their expansion might have resulted from exposure to foreign antigens or superantigens. In contrast, V delta 1+ T cells in PBL showed no comparable increase in relative numbers and were either negative or expressed only low levels of CD45RO. Consistent with evidence for extrathymic peripheral expansion of selective TCR-gamma/delta subsets, no link between MHC haplotype and differences in the TCR-gamma/delta V gene usage between individuals was apparent, and identical twins displayed TCR-gamma/delta variable gene segment phenotypes that were strikingly different from one another. The elements that determine the TCR-gamma/delta repertoire in individuals are not known. It is possible that both thymic selection and extrathymic factors may influence the peripheral repertoire. Recently, TCR-gamma/delta+ lymphocytes have been shown to expand markedly in peripheral lymphoid tissues and infectious lesions in response to mycobacterial antigens, and a correlation between mycobacterial responses and TCR-gamma/delta V gene usage has been shown in mice. The data presented here demonstrated peripheral age-related changes in the gamma/delta repertoire and point to the importance of extrathymic expansion of specific gamma/delta subsets in generating the human TCR-gamma/delta repertoire.

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