Peripheral blood γδ T cells in human listeriosis

Bertotto, A; Spinozzi, Fabrizio; Gerli, Roberto; Bassotti, Gabrio; Forenza, N; Vagliasindi, C; Vaccaro, R

doi:10.1111/j.1651-2227.1995.tb13584.x

Cited by 9 publications

(8 citation statements)

References 6 publications

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“…8) (62, 63). Similar expansions are noted with infections with Listeria monocytogenes (67, 68) and with Brucella melitensis after ingestion of contaminated milk (69). Moreover, during tularemia infection (due to Francisella tularensis ), circulating Vγ2Vδ2 T cells increase as early as 1 wk with levels 2 wks postinfection between 22 and 50% of the circulating T cells (70).…”

Section: Discussionsupporting

confidence: 63%

Metabolic Engineering of Salmonella Vaccine Bacteria To Boost Human Vγ2Vδ2 T Cell Immunity

Workalemahu

Wang

Puan

et al. 2014

The Journal of Immunology

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Human Vγ2Vδ2 T cells monitor isoprenoid metabolism by recognizing foreign (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a metabolite in the 2-C-methyl-D-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate pathway used by humans. Whereas microbial infections elicit prolonged expansion of memory Vγ2Vδ2 T cells, immunization with prenyl pyrophosphates or aminobisphosphonates elicit short-term Vγ2Vδ2 expansion with rapid anergy and deletion upon subsequent immunizations. We hypothesized that a live, attenuated bacterial vaccine that overproduces HMBPP would elicit long lasting Vγ2Vδ2 T cell immunity by mimicking a natural infection. Therefore, we metabolically engineered the avirulent aroA− Salmonella enterica serovar Typhimurium SL7207 strain by deleting the gene for LytB (the downstream enzyme from HMBPP) and functionally complementing for this loss with genes encoding mevalonate pathway enzymes. LytB− Salmonella SL7207 had high HMBPP levels, infected human cells as efficiently as the wild-type bacteria, and stimulated large ex vivo expansions of Vγ2Vδ2 T cells from human donors. Importantly, vaccination of a rhesus monkey with live lytB− Salmonella SL7207 stimulated a prolonged expansion of Vγ2Vδ2 T cells without significant side effects or anergy induction. These studies provide proof-of-principle that metabolic engineering can be used to derive live bacterial vaccines that boost Vγ2Vδ2 T cell immunity. Similar engineering of metabolic pathways to produce lipid Ags or B vitamin metabolite Ags could be used to derive live bacterial vaccine for other unconventional T cells that recognize nonpeptide Ags.

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Section: Discussionsupporting

confidence: 63%

Metabolic Engineering of Salmonella Vaccine Bacteria To Boost Human Vγ2Vδ2 T Cell Immunity

Workalemahu

Wang

Puan

et al. 2014

The Journal of Immunology

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“…Hints at an important role for γδ T cells in immunity come from the observed large expansions of these cells that occur in response to a wide range of pathogens. In humans, bacterial infections including Mycobacterium tuberculosis [4], Mycobacterium leprae [5], Salmonella typi [6], Brucella melitensis [7], Francisella tularensis [8], Listeria monocytogenes [9,10] and Ehrlichia chaffeensis [11], viral infections including HIV [12–14], Epstein‐Barr Virus [15] and cytomegalovirus [16,17], yeast infection with Candida albicans [18] and parasitic infections including Plasmodium falciparum [19], Plasmodium vivax [20] and Leishmania donovani [21] can all stimulate a dramatic expansion of γδ T cells in vivo . While murine studies have shown that γδ T cells are redundant and nonessential for immunity to many infectious agents (reviewed in [1]) they are indispensable and nonredundant for immunity to other pathogens.…”

Section: Introductionmentioning

confidence: 99%

Recognition of nonpeptide antigens by human Vγ9Vδ2 T cells requires contact with cells of human origin

Green¹,

Lissina²,

Hutchinson³

et al. 2004

Clinical and Experimental Immunology

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SUMMARYIt is becoming apparent that gd T cells form an important part of the adaptive immune response. However, the ligands recognized by gd T cell receptors (TCRs) and the exact biological function of the cells that express this receptor remain unclear. Numerous studies have shown that the dominant human peripheral blood subset of gd T cells, which express a V g 9V d 2 TCR, can activate in response to low molecular weight nonpeptidic molecules. Some of these components have been purified from bacteria or parasites. We examined the activation of polyclonal gd T cell lines, clones with V g 9V d 2 and V g 9V d 1 TCRs, and gd T cells directly ex vivo in response to multiple phosphate, alkylamine and aminobisphosphonate (nBP) antigens and purified protein derivative from Mycobacterium tuberculosis (PPD). V g 9V d 2 T cells were able to respond to multiple small organic molecules of highly variable structure whereas cells expressing a similar V g 9 chain paired with a V d 1 chain failed to recognize these antigens. Thus, the TCR d chain appears to make an important contribution to the recognition of these antigens. The kinetics of responses to alkylphosphate and alkylamine antigens differ from those of responses to the nBP pamidronate. These different classes of antigen are believed to have differed mechanisms of action. Such differences explain why nBPs can be pulsed onto antigen presenting cells (APCs) and still retain their ability to activate gd T cells while alkylphosphate and alkylamine antigens cannot. We also demonstrate that a substantial proportion of the cells that produce IFN g directly ex vivo in response to PPD are gd T cells and that gd T cell activation requires contact with cells of human origin.

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“…44 Expansion of T lymphocyte populations in response to pathogens, such as Plasmodium falciparum, Listeria monocytogenes, and cytomegalovirus, among others, has been observed by several studies. [45][46][47] Moreover, changes in circulating T lymphocyte subpopulations were observed in HIV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers

Albuquerque

Granato

Castro

et al. 2019

Journal of Leukocyte Biology

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Human T‐cell lymphotropic virus type‐1 (HTLV‐1) is the etiologic agent of HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV‐1 proviral load. Gamma‐delta T lymphocytes have been recognized as important players in a variety of infectious diseases. Therefore, we have investigated interactions between HTLV‐1 infection and γδ T lymphocytes during HAM/TSP. Similar frequencies of total γδ T lymphocytes and their Vγ9δ2+ and Vγ9δ2neg subpopulations were observed in HAM/TSP patients. However, T lymphocytes obtained from HTLV‐1 carriers displayed significantly higher rates of spontaneous proliferation and NKp30 expression when compared to cells from uninfected donors. In addition, an important decrease in the frequency of granzyme B+ γδ T lymphocytes (approximately 50%) was observed in HAM/TSP patients. Higher proportion of IFN‐γ+ γδ T lymphocytes was found in HTLV‐1‐infected patients, which positively correlated with the HTLV‐1 proviral load in peripheral blood mononuclear cells. Collectively, our data indicates that HTLV‐1 infection leads to phenotypic and functional changes in the population of γδ T lymphocyte population, suggesting that HTLV‐1 infection modulates functions associated to these cells, which might be involved in controlling the infection or in the development of HTLV‐1‐associated diseases.

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Peripheral blood γδ T cells in human listeriosis

Cited by 9 publications

References 6 publications

Metabolic Engineering of Salmonella Vaccine Bacteria To Boost Human Vγ2Vδ2 T Cell Immunity

Metabolic Engineering of Salmonella Vaccine Bacteria To Boost Human Vγ2Vδ2 T Cell Immunity

Recognition of nonpeptide antigens by human Vγ9Vδ2 T cells requires contact with cells of human origin

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers

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