The Interplay between Cytokines and T Cells in Immunity to Intracellular Bacteria

Author(s):  
Stefan H. E. Kaufmann
1986 ◽  
Vol 164 (1) ◽  
pp. 363-368 ◽  
Author(s):  
S H Kaufmann ◽  
E Hug ◽  
G De Libero

Lyt-2+ T cell clones were established from Listeria monocytogenes-infected mice. The clones secreted IFN-gamma after stimulation with spleen cells from L. monocytogenes-infected mice plus IL-2. Spleen cells from normal mice were not stimulatory. Furthermore, cloned T cells lysed L. monocytogenes-infected macrophages. Cytolysis was antigen-specific and H-2K-restricted. These findings suggest a role for specific cytotoxic T cells in the immune response to intracellular bacteria.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Zihao Mi ◽  
Zhenzhen Wang ◽  
Xiaotong Xue ◽  
Tingting Liu ◽  
Chuan Wang ◽  
...  

AbstractLepromatous leprosy (L-LEP), caused by the massive proliferation of Mycobacterium leprae primarily in macrophages, is an ideal disease model for investigating the molecular mechanism of intracellular bacteria evading or modulating host immune response. Here, we performed single-cell RNA sequencing of both skin biopsies and peripheral blood mononuclear cells (PBMCs) of L-LEP patients and healthy controls. In L-LEP lesions, we revealed remarkable upregulation of APOE expression that showed a negative correlation with the major histocompatibility complex II gene HLA-DQB2 and MIF, which encodes a pro-inflammatory and anti-microbial cytokine, in the subset of macrophages exhibiting a high expression level of LIPA. The exhaustion of CD8+ T cells featured by the high expression of TIGIT and LAG3 in L-LEP lesions was demonstrated. Moreover, remarkable enhancement of inhibitory immune receptors mediated crosstalk between skin immune cells was observed in L-LEP lesions. For PBMCs, a high expression level of APOE in the HLA-DRhighFBP1high monocyte subset and the expansion of regulatory T cells were found to be associated with L-LEP. These findings revealed the primary suppressive landscape in the L-LEP patients, providing potential targets for the intervention of intracellular bacteria caused persistent infections.


2005 ◽  
Vol 174 (9) ◽  
pp. 5341-5350 ◽  
Author(s):  
Henk van Faassen ◽  
Marsha Saldanha ◽  
Deanna Gilbertson ◽  
Renu Dudani ◽  
Lakshmi Krishnan ◽  
...  

2011 ◽  
Vol 41 (6) ◽  
pp. 1619-1628 ◽  
Author(s):  
Stéphanie Bessoles ◽  
Ming Ni ◽  
Sara Garcia-Jimenez ◽  
Françoise Sanchez ◽  
Virginie Lafont

2005 ◽  
Vol 202 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Siobhán C. Cowley ◽  
Elizabeth Hamilton ◽  
Jeffrey A. Frelinger ◽  
Jie Su ◽  
James Forman ◽  
...  

Memory T cells, including the well-known CD4+ and CD8+ T cells, are central components of the acquired immune system and are the basis for successful vaccination. After infection, CD4+ and CD8+ T cells expand into effector cells, and then differentiate into long-lived memory cells. We show that a rare population of CD4−CD8−CD3+αβ+γδ−NK1.1− T cells has similar functions. These cells potently and specifically inhibit the growth of the intracellular bacteria Mycobacterium tuberculosis (M. tb.) or Francisella tularensis Live Vaccine Strain (LVS) in macrophages in vitro, promote survival of mice infected with these organisms in vivo, and adoptively transfer immunity to F. tularensis LVS. Furthermore, these cells expand in the spleens of mice infected with M. tb. or F. tularensis LVS, and then acquire a memory cell phenotype. Thus, CD4−CD8− T cells have a role in the control of intracellular infection and may contribute to successful vaccination.


1999 ◽  
Vol 11 (1) ◽  
pp. 89-93 ◽  
Author(s):  
John T Harty ◽  
Michael J Bevan

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11524 ◽  
Author(s):  
Marc Bajénoff ◽  
Emilie Narni-Mancinelli ◽  
Frédéric Brau ◽  
Grégoire Lauvau

2004 ◽  
Vol 78 (8) ◽  
pp. 4020-4028 ◽  
Author(s):  
Henning Lauterbach ◽  
Kristen M. Kerksiek ◽  
Dirk H. Busch ◽  
Elena Berto ◽  
Aleksandra Bozac ◽  
...  

ABSTRACT Adaptive immune responses in which CD8+ T cells recognize pathogen-derived peptides in the context of major histocompatibility complex class I molecules play a major role in the host defense against infection with intracellular pathogens. Cells infected with intracellular bacteria such as Listeria monocytogenes, Salmonella enterica serovar Typhimurium, or Mycobacterium tuberculosis are directly lysed by cytotoxic CD8+ T cells. For this reason, current vaccines for intracellular pathogens, such as subunit vaccines or viable bacterial vaccines, aim to generate robust cytotoxic T-cell responses. In order to investigate the capacity of a herpes simplex virus type 1 (HSV-1) vector to induce strong cytotoxic effector cell responses and protection from infection with intracellular pathogens, we developed a replication-deficient, recombinant HSV-1 (rHSV-1) vaccine. We demonstrate in side-by-side comparison with DNA vaccination that rHSV-1 vaccination induces very strong CD8+ effector T-cell responses. While both vaccines provided protection from infection with L. monocytogenes at low, but lethal doses, only rHSV-1 vaccines could protect from higher infectious doses; HSV-1 induced potent memory cytotoxic T lymphocytes that, upon challenge by pathogens, efficiently protected the animals. Despite the stimulation of relatively low humoral and CD4-T-cell responses, rHSV-1 vectors are strong candidates for future vaccine strategies that confer efficient protection from subsequent infection with intracellular bacteria.


2020 ◽  
Author(s):  
Md. Yeashin Gazi ◽  
Yuji Takeda ◽  
Hidetoshi Nara ◽  
Akemi Araki ◽  
Nobuhito Nemoto ◽  
...  

Abstract Background/Purpose: Interleukin-21 (IL-21), which is a member of the common γ-chain cytokine family, is mainly produced by CD4+ T cells and has broad impact on immune responses. IL-21 isoform is a splicing variant of IL-21 and is functionally similar to conventional IL-21. We established IL-21 isoform transgenic (IL-21isoTg) mouse, which constitutively expresses IL-21 isoform specifically in T cells. IL-21isoTg mouse possesses high amount of CD8+ T cells in normal physiological condition. The purpose of this study is to determine whether CD8+ T cells in the IL-21isoTg mouse work against intracellular bacteria infection.Methods: Wild type (WT) and IL-21isoTg mouse are orally inoculated Listeria monocytogenes (L. monocytogenes) on day 0, and 15 days after primary infection. Bacterial load in each organs, and T cell responses are analyzed.Results: IL-21isoTg and wild type (WT) mouse had similar bacterial load after L. monocytogenes primary infection. On the other hand, after secondary challenge infection, IL-21isoTg mouse exhibited reduced bacterial load in some organs compared to WT. Analysis of T cell response after primary infection showed that IL-21isoTg mouse induced higher levels of CD8+ effector memory T (TEM) cells than WT.Conclusion: IL-21-induced CD8+ TEM cells might eventually reduce the bacterial load in organs after secondary challenge infection in IL-21isoTg mouse. To the best of our knowledge, this is the first study to show that IL-21 is a pivotal factor involved in eliminating intracellular bacteria, probably through CD8+ TEM cells.


2000 ◽  
Vol 8 (9) ◽  
pp. 419-425 ◽  
Author(s):  
Ulrich E. Schaible ◽  
Stefan H.E. Kaufmann

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