scholarly journals CHARACTERISTICS OF CELLULAR COMPARTMENT CHANGES OF IMMUNE SYSTEM IN THE PATIENTS WITH CHRONIC POLYPOUS RHINOSINUSITIS DEPEND ON EFFICIENCY OF DRUG THERAPY

2019 ◽  
Vol 21 (4) ◽  
pp. 715-724
Author(s):  
E. L. Savlevich ◽  
A. V. Zurochka ◽  
S. V. Khaidukov
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Drug Therapy ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Nasal Polyps ◽  
Inflammatory Process ◽  
Nkt Cells ◽  
Absolute Number ◽  
Effector Cells

Despite numerous attempts to control the course of chronic rhinosinusitis with nasal polyps (CRSwNP) by means of pharmacological treatment and new surgical approaches, the majority of patients experience lifelong persistence of this disorder, at recurrence rates of 50-60% within 18 months after surgical treatment. Since CRSwNP is a chronic persistent inflammatory process, it affects the entire body condition, including the state of systemic immune response. An elevation of NK (CD3-CD16+CD56+), activated NK (CD8+CD3-), NKT cells (CD16+CD56+CD3+), Treg (CD4+CD25brightCD127low to neg) cells and activated T-lymphocytes (CD3+CD25+) was revealed elsewhere among all the patients with CRSwNP, using a flow ytometry method. There was no difference between various disease phenotypes. We analyzed the status of cellular component of systemic immunity, dependent on clinical course of the disease and efficiency of the administered therapy of CRSwNP. The patients were divided into three subgroups. The follow-up period was 1 year. The first group comprised the patients who showed positive dynamics after conservative therapy, resulting into regression of nasal polyps and their grade than a year ago. The second group included the patients in whom the size of polyps remained the same. The third group included the patients with higher incidence of nasal polyps than a year ago.We have shown a decrease of Treg, NKT cells, NK and activated NK, cytotoxic T-lymphocytes (CD3+CD8+), activated T-cell numbers in clinical group 3 with aggressive growth of polyps and low effect of standard therapy, which may cause deterioration of the immune system cellular populations, accompanied by presence of persistent productive inflammatory process of nasal cavity and paranasal sinuses. In the second group, a significant elevation of total lymphocyte number, total and activated T cells, T helpers (CD3+CD4+), cytotoxic T lymphocytes, NK and NKT cells was shown. Meanwhile, a decrease in absolute number of activated NK was observed despite the NK growth. Therefore, we can assume that the mechanism of their activation was disturbed and compensated by production of NKT cells and cytotoxic T lymphocytes. Moreover, we have shown in this group that the absolute number of Treg cells is increased; and these cells had a suppressive influence on effector cells of adaptive immune response, thus inducing incomplete elimination of infectious agents, which contribute to permanent incomplete course of inflammatory process. Chronic inflammatory process in CRSwNP affects systemic cellular immunity depending on the morbidity characteristics in the course of pathological process. The maximal intensity of systemic cellular immunity is observed in the group of patients that require permanent basic drug therapy. In case of aggressive CRSwNP and failure of standard drug therapy, we observed a decrease in absolute numbers of effector cells, along with decreased Treg lymphocyte numbers which may explain inefficient immune regulation of inflammatory process and medical interventions in this group of patients.

Caffeine-enhanced anti-tumor immune response through decreased expression of PD1 on infiltrated cytotoxic T lymphocytes

2019 ◽  
Vol 859 ◽  
pp. 172538 ◽  
Author(s):  
Gullanki Naga Venkata Charan Tej ◽  
Kaushik Neogi ◽  
Sumit Singh Verma ◽  
Subash Chandra Gupta ◽  
Prasanta Kumar Nayak
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals Combining PARP inhibition, radiation, and immunotherapy: A possible strategy to improve the treatment of cancer?

2018 ◽  
Vol 19 (12) ◽  
pp. 3793 ◽  
Author(s):  
Mathieu Césaire ◽  
Juliette Thariat ◽  
Serge M. Candéias ◽  
Dinu Stefan ◽  
Yannick Saintigny ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiation Therapy ◽  
T Lymphocytes ◽  
Ionizing Radiation ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Antitumor Immune Response ◽  
Parp Inhibition

Immunotherapy has revolutionized the practice of oncology, improving survival in certain groups of patients with cancer. Immunotherapy can synergize with radiation therapy, increase locoregional control, and have abscopal effects. Combining it with other treatments, such as targeted therapies, is a promising means of improving the efficacy of immunotherapy. Because the value of immunotherapy is amplified with the expression of tumor antigens, coupling poly(ADP-ribose) polymerase (PARP) inhibitors and immunotherapy might be a promising treatment for cancer. Further, PARP inhibitors (PARPis) are being combined with radiation therapy to inhibit DNA repair functions, thus enhancing the effects of radiation; this association might interact with the antitumor immune response. Cytotoxic T lymphocytes are central to the antitumor immune response. PARP inhibitors and ionizing radiation can enhance the infiltration of cytotoxic T lymphocytes into the tumor bed, but they can also enhance PD-1/PDL-1 expression. Thus, the addition of immune checkpoint inhibitors with PARP inhibitors and/or ionizing radiation could counterbalance such immunosuppressive effects. With the present review article, we proposed to evaluate some of these associated therapies, and we explored the biological mechanisms and medical benefits of the potential combination of radiation therapy, immunotherapy, and PARP inhibitors.

scholarly journals Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes

2019 ◽  
Vol 30 (7) ◽  
pp. 2049-2059 ◽  
Author(s):  
Neha Nandedkar-Kulkarni ◽  
Abhishek R. Vartak ◽  
Steven J. Sucheck ◽  
Katherine A. Wall ◽  
Anthony Quinn ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals Subsets of Memory Cytotoxic T Lymphocytes Elicited by Vaccination Influence the Efficiency of Secondary Expansion In Vivo

2004 ◽  
Vol 78 (1) ◽  
pp. 206-215 ◽  
Author(s):  
Michael S. Seaman ◽  
Fred W. Peyerl ◽  
Shawn S. Jackson ◽  
Michelle A. Lifton ◽  
Darci A. Gorgone ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Memory T Cells ◽  
Central Memory ◽  
Effector Memory ◽  
Interleukin 12 ◽  
Effector Cells ◽  
Memory Cytotoxic T Lymphocytes

ABSTRACT Vaccine-elicited cytotoxic T lymphocytes (CTL) should be long-lived memory cells that can rapidly expand in number following re-exposure to antigen. The present studies were initiated to analyze the ability of plasmid interleukin-12 (IL-12) to augment CTL responses in mice when delivered during the peak phase of an immune response elicited by a plasmid human immunodeficiency virus type 1 gp120 DNA vaccine. Delivery of plasmid IL-12 on day 10 postimmunization resulted in a robust expansion of gp120-specific CD8+ T cells, as measured by tetramer, gamma interferon ELISPOT, and functional-killing assays. Interestingly, this delayed administration of plasmid IL-12 had no significant effect on antigen-specific CD4+-T-cell and antibody responses. Phenotypic analyses suggested that administration of plasmid IL-12 near the time of the peak CTL response activated and expanded antigen-specific effector cells, preventing their loss through apoptosis. However, this IL-12-augmented population of gp120-specific CD8+ T cells did not efficiently expand following gp120 boost immunization, suggesting that these effector cells would be of little utility in expanding to contain a viral infection. Analyses of the phenotypic profile and anatomic distribution of the plasmid IL-12-augmented CTL population indicated that these lymphocytes were primarily effector memory rather than central memory T cells. These observations suggest that CTL-based vaccines should elicit central memory rather than effector memory T cells and illustrate the importance of monitoring the phenotype and functionality of vaccine-induced, antigen-specific CTL.

Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection*

1999 ◽  
Vol 97 (6) ◽  
pp. 707-718 ◽  
Author(s):  
David A. PRICE ◽  
Chris A. O'CALLAGHAN ◽  
Joseph A. WHELAN ◽  
Philippa J. EASTERBROOK ◽  
Rodney E. PHILLIPS
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Evolution ◽  
Case Series ◽  
Effector Cells ◽  
Lymphocyte Responses ◽  
Hiv 1

Efforts to develop immune-based therapies for HIV infection have been impeded by incomplete definition of the immunological correlates of protection. Despite many precedents demonstrating that CD8+ cytotoxic T lymphocytes are key mediators of protective anti-viral immunity in non-human animal models, direct evidence that these effector cells control viral replication in HIV-1 infection has remained elusive. The first part of this paper describes a detailed immunological and genetic study founded on evolutionary considerations. Following infection with HIV-1, virus variants which escaped recognition by autologous cytotoxic T lymphocytes were shown to possess a selection advantage within the host environment. Cytotoxic T lymphocytes therefore exert anti-viral pressure in vivo. This observation provides compelling evidence that cytotoxic T lymphocytes comprise a significant element of anti-retroviral immunity. Subsequently, the quantification of peripheral cytotoxic T lymphocyte frequencies utilizing peptide–(human leucocyte antigen class I) tetrameric complexes is described. Five patients with qualitatively similar immunodominant cytotoxic T lymphocyte responses during symptomatic primary HIV-1 infection were studied longitudinally. Expansions of virus-specific CD8+ lymphocytes comprising up to 2% of the total CD8+ T cell population were observed in the acute phase of infection. Antigenic load was identified as an important determinant of circulating HIV-1-specific CD8+ lymphocyte levels; however, significant numbers of such cells were also found to persist following prolonged therapeutic suppression of plasma viraemia. In addition, an analysis of antigenic sequence variation with time in this case series suggests that the early administration of combination anti-retroviral therapy may limit HIV-1 mutational escape from host cytolytic specificities. The implications of these preliminary data are discussed. The data presented suggest that vaccination protocols should aim to elicit vigorous cytotoxic T lymphocyte responses to HIV-1. Attempts to stimulate polyvalent responses to mutationally intolerant epitopes are likely to be most effective. Optimal management of HIV-1 infection requires an understanding of dynamic host–virus interactions, and may involve strategies designed to enhance cytotoxic T lymphocyte activity following periods of anti-retroviral drug therapy.

scholarly journals DISCORDANT RESPONSE OF CD4+ T LYMPHOCYTES TO ANTIRETROVIRAL THERAPY

2019 ◽  
Vol 11 (1) ◽  
pp. 16-30 ◽  
Author(s):  
K. V. Shmagel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Viral Load ◽  
Immune System ◽  
Antiretroviral Therapy ◽  
T Lymphocytes ◽  
Lymphocyte Proliferation ◽  
Immune Reconstitution ◽  
Cell Counts ◽  
Increased Risk

Antiretroviral therapy (ART) in HIV infected patients generally results in the suppression of viral replication and reconstitution of CD4+ T lymphocytes cell counts. In some patients (about 20%), however, a disturbance in regeneration of immune competent cells with a background of low viral load occurs. The term «immunological nonresponders» has been used to describe this phenomenon. Discordant immune response to antiviral therapy may be caused by increasing of depletion and reducing of production of CD4+ T cells. However, mechanisms for low immune reconstitution are not currently well understood. «Immunological nonresponders» exhibit booster lymphocyte proliferation, increased immune activation and reducing of CD4+ T lymphocytes survival time in comparison with patients with concordant response to the therapy. Their immune system is characterized by more pronounced aging and exhaustion. This leads to early and frequent manifestation of AIDSrelated diseases. Besides, immunological nonresponders have an increased risk of non-AIDS-related diseases due to pronounced systemic inflammation. The objective of the present review was to highlight the important problem that is rather common on аntiretroviral therapy and to enlist the specialists to the solving of this issue.

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