In vivo depletion of CD4 and CD8 T lymphocytes impairs Mycobacterium w vaccine-induced protection against M. tubercolosis in mice

1993 ◽  
Vol 182 (3) ◽  
Author(s):  
Indira Guleria ◽  
Rama Mukherjee ◽  
StefanH.E. Kaufmann
BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Guoping Ding ◽  
Tao Shen ◽  
Chen Yan ◽  
Mingjie Zhang ◽  
Zhengrong Wu ◽  
...  

Abstract Background Pancreatic cancer is characterized by a highly immunosuppressive tumor microenvironment and evasion of immune surveillance. Although programmed cell death 1 receptor (PD-1) blockade has achieved certain success in immunogenic cancers, the responses to the PD-1 antibody are not effective or sustained in patients with pancreatic cancer. Methods Firstly, PD-1 expressions on peripheral CD8+ T-lymphocytes of patients with pancreatic cancer and healthy donors were measured. In in vitro study, peripheral T-lymphocytes were isolated and treated with nivolumab and/or interferon-γ, and next, PD-1-blockade effects, proliferations, cytokine secretions and cytotoxic activities were tested after different treatments. In in vivo study, mice bearing subcutaneous pancreatic cancer cell lines were treated with induced T-lymphocytes and tumor sizes were measured. Results PD-1 protein expression is increased on peripheral CD8+ T cells in patients with pancreatic ductal adenocarcinoma compared with that in health donor. PD-1 expression on CD8+ T-lymphocytes was decreased by nivolumab in a concentration-dependent manner in vitro. IFN-γ could directly down-regulate expression of PD-1 in vitro. Furthermore, the combination therapy of nivolumab and IFN-γ resulted in greatest effect of PD-1-blockde (1.73 ± 0.78), compared with IFN-γ along (18.63 ± 0.82) and nivolumab along (13.65 ± 1.22). Moreover, the effects of nivolumab plus IFN-γ largest promoted the T-lymphocytes function of proliferations, cytokine secretions and cytotoxic activities. Most importantly, T-lymphocytes induced by nivolumab plus IFN-γ presented the best repression of tumor growth. Conclusions IFN-γ plus a PD-1-blockading agent could enhance the immunologic function and might play a crucial role in effective adoptive transfer treatments of pancreatic cancer.


Virology ◽  
2009 ◽  
Vol 386 (2) ◽  
pp. 380-386 ◽  
Author(s):  
Yvonne Drechsler ◽  
Ryan L. Bohls ◽  
Roger Smith ◽  
Nova Silvy ◽  
Hyun Lillehoj ◽  
...  

2005 ◽  
Vol 28 (4) ◽  
pp. 343-351 ◽  
Author(s):  
Paul J Hensbergen ◽  
Pepijn G. J. T. B Wijnands ◽  
Marco W. J Schreurs ◽  
Rik J Scheper ◽  
Rein Willemze ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 262-270 ◽  
Author(s):  
Sharat Srinivasula ◽  
Richard A. Lempicki ◽  
Joseph W. Adelsberger ◽  
Chiung-Yu Huang ◽  
Joshua Roark ◽  
...  

Abstract We previously showed that HIV infection leads to expansion of a rapidly proliferating pool (s1) of CD4 and CD8 T lymphocytes. In the current study, we used in vivo labeling with bromodeoxyuridine to characterize the kinetics of naive, memory, and activated (HLA-DR+/CD38+) subpopulations of CD4 and CD8 T lymphocytes, and to examine the relationship between kinetic parameters and baseline CD4 counts, HIV viral load, potential markers of microbial translocation, and cytokine levels. Activated cells showed the highest proliferation rates, followed by effector and central memory cells, with naive cells showing the lowest rates, for both CD4 and CD8 T cells. HIV viral load correlated with s1 of CD4 and CD8 effector memory cells, as well as CD8 naive cells, whereas CD4 cell counts correlated inversely with naive CD4 s1. Endotoxin levels showed a weak negative association with CD4 but not CD8 s1. INF-γ and TNF-α were associated with s1 for CD4 and CD8 cells, respectively. Thus, HIV is the primary driving force behind the activation and proliferation of most subsets of both CD4 and CD8 T lymphocytes, whereas naive CD4 cell proliferation likely represents a homeostatic response. Microbial translocation does not appear to play an important role in this proliferation.


2007 ◽  
Vol 179 (10) ◽  
pp. 6725-6733 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Michael W. Panas ◽  
Shaila Rahman ◽  
Piya Sircar ◽  
Geoffrey Gillard ◽  
...  

2001 ◽  
Vol 194 (9) ◽  
pp. 1339-1348 ◽  
Author(s):  
Xingluo Liu ◽  
Xue-Feng Bai ◽  
Jing Wen ◽  
Jian-Xin Gao ◽  
Jinqing Liu ◽  
...  

B7H/B7RP (hereby called B7H) is a new member of the B7 family of costimulatory molecules and interacts with inducible costimulatory molecule (ICOS). Its function for CD8 T cells has not been reported. We report here that expression of B7H on the tumor cells reduced tumorigenicity and induced immunity to subsequent challenge with parental tumor cells. The immune protection correlates with an enhanced cytotoxic T lymphocyte (CTL) response against P1A, the major tumor antigen expressed in the J558 tumor. To understand the mechanism of immune protection, we adoptively transferred transgenic T cells specific for tumor antigen P1A into mice that bore P1A-expressing tumors. We found that while the transgenic T cells divided faster in mice bearing the B7H+ tumors, optimal B7H-induced clonal expansion of P1CTL required costimulation by B7–1 and B7–2 on the endogenous host antigen-presenting cells (APCs). Interestingly, when B7H+ and B7H− tumors were coinjected, P1CTL selectively eliminated the B7H+ tumor cells. Moreover, B7H expressed on the tumor cells made them highly susceptible to destruction by CTL in vivo, even if the CTL was administrated into mice with large tumor burdens. Tumors that recurred in the P1CTL-treated mice lost transfected B7H and/or H-2Ld, the class I molecule that presents the P1A peptide. Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8+ T lymphocytes in vivo.


2013 ◽  
Vol 1 (S1) ◽  
Author(s):  
Carina Wehner ◽  
Christian Ellinger ◽  
Silke Raffegerst ◽  
Susanne Wilde ◽  
Barbara Mosetter ◽  
...  

2005 ◽  
Vol 86 (9) ◽  
pp. 2445-2450 ◽  
Author(s):  
C. A. L. Oura ◽  
M. S. Denyer ◽  
H. Takamatsu ◽  
R. M. E. Parkhouse

To understand the mechanisms involved in protective immunity to African swine fever virus (ASFV) infection, the observation that infection with the avirulent Portuguese ASFV isolate OUR/T88/3 protects outbred pigs from challenge with the virulent Portuguese ASFV isolate OUR/T88/1 was exploited. It was demonstrated that pigs exposed to OUR/T88/3 and then depleted of CD8+ lymphocytes were no longer fully protected from OUR/T88/1 challenge. This indicated that CD8+ lymphocytes play an important role in the protective immune response to ASFV infection and that anti-ASFV antibody alone, from OUR/T88/3 infection, was not sufficient to protect pigs from OUR/T88/1 challenge. Inbred pigs of the cc haplotype infected with OUR/T88/3 were not always protected from OUR/T88/1 challenge and developed both viraemia and fever. Such viraemia was always correlated with increased numbers of circulating CD8β + lymphocytes, indicating a specific role for CD8β + lymphocytes in combating viraemia. These experiments indicate an important role for CD8+ lymphocytes, particularly CD8β + lymphocytes, in ASF protective immunity.


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