scholarly journals Depletion of the programmed death-1 receptor completely reverses established clonal anergy in CD4+ T lymphocytes via an interleukin-2-dependent mechanism

2009 ◽  
Vol 256 (1-2) ◽  
pp. 86-91 ◽  
Author(s):  
Kenneth D. Bishop ◽  
John E. Harris ◽  
John P. Mordes ◽  
Dale L. Greiner ◽  
Aldo A. Rossini ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Interleukin 2 ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Dependent Mechanism ◽  
Clonal Anergy

scholarly journals UV irradiation can induce in vitro clonal anergy in alloreactive cytotoxic T lymphocytes

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 176-181 ◽  
Author(s):  
T Kobata ◽  
H Ikeda ◽  
Y Ohnishi ◽  
N Urushibara ◽  
TA Takahashi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Calcium Ionophore ◽  
Target Cells ◽  
Ionophore A23187 ◽  
Peripheral Blood Mononuclear ◽  
High Affinity ◽  
Clonal Anergy

The alloreactive cytotoxic T lymphocytes (CTL) were generated by coculturing peripheral blood mononuclear cells (PBMC) with allogeneic Sa cells (an Epstein-Barr virus [EBV]-transformed B-cell line). The CTL did not proliferate in response to UV-B-irradiated Sa cells unless exogenous interleukin-2 (IL-2) was present, although they could kill the UV-B-irradiated Sa cells. The results indicate that UV-B-irradiated Sa cells do not provide sufficient signals for the proliferation of the CTL while they can be recognized by CTL and induce high-affinity IL-2 receptor (IL-2R) expression on them. The alloreactive CTL could be rendered anergic by previous exposure to UV-B-irradiated Sa cells. The alloreactive CTL previously stimulated with UV-B-irradiated Sa cells failed to proliferate in response to nontreated Sa cells. Proliferation of the anergic CTL could not be restored by Sa cells and exogenous IL-2 but by the combination of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). The anergic CTL showed a considerably low cytotoxic activity against Sa target cells. The expression of TCR on the anergic CTL was downregulated while expression of high-affinity IL- 2R was upregulated. Their CD28 and CD8 expression were unchanged. In addition, the proliferative response and cytotoxicity of the anergic CTL to Sa cells could be restored after the cells had been rested for 7 days to allow reexpression of TCR. These results suggest that downregulation of T-cell receptor (TCR) and impairment in the post-IL- 2/IL-2R signaling pathway are relevant to the clonal anergy induced in the alloreactive CTL by stimulation of UV-B-irradiated Sa cells.

scholarly journals "Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype.

1994 ◽  
Vol 179 (2) ◽  
pp. 481-491 ◽  
Author(s):  
T F Gajewski ◽  
D W Lancki ◽  
R Stack ◽  
F W Fitch
Keyword(s):  
T Lymphocytes ◽  
Interleukin 2 ◽  
Substantial Reduction ◽  
Cell Receptor ◽  
Cytolytic Activity ◽  
Precursor Cell ◽  
Th2 Cells ◽  
Free Calcium ◽  
Helper T Lymphocytes ◽  
Clonal Anergy

Mature CD4+ helper T lymphocytes have been categorized into two major functional phenotypes, TH1 and TH2, which produce distinct arrays of lymphokines and which are thought to arise from a pluripotential precursor cell termed TH0. Clonal anergy can be induced in TH1 clones by stimulating via the T cell receptor (TCR) complex in the absence of a costimulator molecule; however, anergy has been difficult to demonstrate in TH2 clones. We show here that treatment of cloned TH0 lines with anergizing stimuli results in the selective loss of TH1 characteristics and retention of a TH2 phenotype. Treated cells exhibit a substantial reduction in interleukin 2 (IL-2) production and antigen-specific cytolytic activity, but retain comparable IL-4 and IL-5 production in response to restimulation via the TCR complex. TH0 clones exposed to anergizing stimuli also increase in size, thus morphologically resembling TH2 cells. The signaling characteristics of these cells also are altered, in that they exhibit an elevated basal level of intracellular free calcium which fails to increase significantly with subsequent restimulation, reminiscent of the signaling characteristics of TH2 cells. "Anergized" TH0 clones thus share several functional, morphologic, and physiologic properties with cells of the TH2 phenotype, suggesting that TH2 cells may arise when TH0 cells are stimulated via the TCR complex in the absence of a putative costimulator molecule.

Activation-Induced Expression of Human Programmed Death-1 Gene in T-Lymphocytes

1997 ◽  
Vol 232 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Rajeev Vibhakar ◽  
Gloria Juan ◽  
Frank Traganos ◽  
Zbigniew Darzynkiewicz ◽  
Lawrence R. Finger
Keyword(s):  
T Lymphocytes ◽  
Induced Expression ◽  
Programmed Death ◽  
Programmed Death 1

PD-L1 Expression in Sarcomas: An Immunohistochemical Study

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S48-S49
Author(s):  
C Cunningham ◽  
J Schnabel ◽  
M Esebua ◽  
L Layfield
Keyword(s):  
T Lymphocytes ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Immunohistochemical Study ◽  
Membrane Staining ◽  
Programmed Death ◽  
Programmed Death 1

Abstract Introduction/Objective Immunotherapy is increasingly used for the treatment of metastatic melanoma and carcinomas. PD-I (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. Methods Fifty-one sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. Results The percentage of each type of sarcoma expressing PD-L1 is reported and 20% of sarcomas expressed PD- L1. The percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. Conclusion PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (20%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies.

scholarly journals The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1730 ◽  
Author(s):  
Ivy Zortéa S. Parise ◽  
Guilherme A. Parise ◽  
Lúcia Noronha ◽  
Mirvat Surakhy ◽  
Thiago Demetrius Woiski ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Ki 67 ◽  
Programmed Death ◽  
Age Of Diagnosis ◽  
Programmed Death 1 ◽  
Adrenocortical Carcinomas ◽  
Cluster Of Differentiation ◽  
And Control

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.

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