Cellular Immune Suppressor Activity Resides in Lymphocyte Cell Clusters Adjacent to Granulomata in Human Coccidioidomycosis

ABSTRACT The in situ immunologic response in human coccidioidomycosis remains undefined. To explore this further, pulmonary necrotizing coccidioidal granulomata were examined using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-γ). Discrete perigranulomatous lymphocytic clusters were seen in eight of nine tissues examined. In these tissues, T lymphocytes (CD3+) significantly outnumbered B lymphocytes (CD20+) in the mantle area of the granulomata (P = 0.028), whereas the clusters were composed of roughly equal numbers of T and B lymphocytes. While the number of cells in the mantle expressing IL-10 was similar to those in the perigranulomatous clusters, there were significantly more cells expressing IFN-γ in the mantle than in the clusters (P = 0.037). Confocal microscopy revealed that CD4+ T lymphocytes and B lymphocytes are associated with IL-10 production. CD4+CD25+ T lymphocytes were identified in the perigranulomatous clusters but were not associated with IL-10 production. This is the first report noting perigranulomatous lymphocyte clusters and IL-10 in association with human coccidioidal granulomata and suggests that down-regulation of the cellular immune response is occurring within coccidioidal granulomata.

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In situ cellular immune response in non-ulcerated skin lesions due to Leishmania (L.) infantum chagasi infection

Journal of Venomous Animals and Toxins including Tropical Diseases ◽

10.1590/1678-9199-jvatitd-2020-0149 ◽

2021 ◽

Cited By ~ 1

Author(s):

Carmen Sandoval ◽

Gabriela Araujo ◽

Wilfredo Sosa ◽

Sara Avalos ◽

Fernando Silveira ◽

...

Keyword(s):

Immune Response ◽

T Lymphocytes ◽

Cutaneous Leishmaniasis ◽

Cellular Immune Response ◽

Defense Mechanisms ◽

Skin Lesions ◽

Cd8 T Lymphocytes ◽

Ifn Γ ◽

Cellular Immune

Background Skin lesions of patients affected by non-ulcerated cutaneous leishmaniasis (NUCL) caused by L. (L.) infantum chagasi are characterized by lymphohistiocytic inflammatory infiltrate associated with epithelioid granuloma and scarce parasitism. However, the in situ cellular immune response of these patients is unclear. Therefore, the aim of the present study was to characterize the cellular immune response in the skin lesions of patients affected by NUCL. Methods Twenty biopsies were processed by immunohistochemistry using primary antibodies to T lymphocytes (CD4, CD8), NK cells, B lymphocytes, macrophages, nitric oxide synthase and interferon-gamma. Results Immunohistochemistry revealed higher expression of all cellular types and molecules (IFN-γ, iNOS) in the dermis of diseased skin compared to the skin of healthy individuals (p < 0.05). Morphometric analysis performed in the skin lesions sections showed the predominance of CD8+ T lymphocytes in the mononuclear infiltrate, followed by macrophages, mostly iNOS+, a response that could be mediated by IFN-γ. Conclusion Our study improves knowledge of the cellular immune response in non-ulcerated or atypical cutaneous leishmaniasis caused by L. (L.) infantum chagasi in Central America and pointed to the pivotal participation of CD8+ T lymphocytes in the host defense mechanisms against the parasite in patients with NUCL.

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Identification and Characterization of a Master Transcription Factor of Th1 Cells, T-bet, Within Flounder (Paralichthys olivaceus)

Frontiers in Immunology ◽

10.3389/fimmu.2021.704324 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hongfei Tian ◽

Jing Xing ◽

Xiaoqian Tang ◽

Heng Chi ◽

Xiuzhen Sheng ◽

...

Keyword(s):

Transcription Factor ◽

T Lymphocytes ◽

B Lymphocytes ◽

T Lymphocyte ◽

Lymphocyte Subsets ◽

Paralichthys Olivaceus ◽

Head Kidney ◽

Edwardsiella Tarda ◽

T Lymphocyte Subsets ◽

Ifn Γ

T-bet, a T-box family member, is a transcription factor essential for the differentiation of naive CD4+ T cells into Th1 cells that are involved in both innate and adaptive immune responses. In this study, the transcription factor T-bet of flounder (Paralichthys olivaceus) was cloned and characterized, and its expression profile after infection was analyzed. T-bet+ cells were identified in flounder, and the expression and localization of T-bet in T lymphocyte subsets and B lymphocytes were investigated. Finally, the proliferation of T-bet+ cells, T lymphocyte subsets, and B lymphocytes were studied after stimulation with IFN-γ, IL-2, and IL-6, respectively, and the variations of some transcription factors and cytokines in CD4+ T lymphocyte subsets were detected. The results showed that T-bet in flounder consists of 619 aa with a conserved T-box DNA binding domain. T-bet was abundantly expressed in the spleen, head kidney, and heart, and it was significantly upregulated after infection with Vibrio anguillarum, Edwardsiella tarda, and Hirame rhabdovirus, especially in the group of Edwardsiella tarda. A polyclonal antibody against recombinant protein of T-bet was prepared, which specifically recognized the natural T-bet molecule in flounder. T-bet+ cells were found to be distributed in the lymphocytes of peripheral blood, spleen, and head kidney, with the highest proportion in spleen, and the positive signals of T-bet occurred in the cell nucleus. T-bet was also detected in the sorted CD4-1+, CD4-2+, CD8+ T lymphocytes, and IgM+ B lymphocytes. In addition, T-bet+ cells, coordinated with CD4-1+ and CD4-2+ T lymphocytes, were proliferated after stimulation with IFN-γ, IL-2, and IL-6. Especially in sorted CD4-1+ and CD4-2+ T lymphocytes, IFN-γ and IL-2 were able to upregulate the expression of T-bet, forming a positive feedback loop in Th1-type cytokine secretion. These results suggest that T-bet may act as a master transcription factor regulating flounder CD4+ T lymphocytes involved in a Th1-type immune response.

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Immunomodulatory consequences of oral administration of Lactobacillus rhamnosus strain GG in healthy volunteers

Journal of Dairy Research ◽

10.1017/s0022029903006034 ◽

2003 ◽

Vol 70 (2) ◽

pp. 165-173 ◽

Cited By ~ 91

Author(s):

Michael Schultz ◽

Hans-Jörg Linde ◽

Norbert Lehn ◽

Kurt Zimmermann ◽

Johannes Grossmann ◽

...

Keyword(s):

T Lymphocytes ◽

Oral Administration ◽

Healthy Volunteers ◽

Intestinal Flora ◽

Lactobacillus Rhamnosus ◽

Cytokine Secretion ◽

Tnf Α ◽

Ifn Γ ◽

Anti Inflammatory ◽

Cellular Immune

Probiotic microorganisms, especially lactic acid bacteria, are effective in the treatment of infectious diarrhoeal diseases and experimental colitis. Although the mechanisms by which these organisms exert their anti-inflammatory effects are largely unknown, immunomodulating effects are suggested. The objective of this study was to examine the effect of a 5-week oral administration of Lactobacillus rhamnosus subspecies GG (Lb. GG) on the cellular immune response to intestinal microorganisms in ten healthy volunteers. Peripheral blood cells (PB) were stimulated with either ‘self’ or ‘non-self’ preparations of faecal samples and isolated Bacteroides fragilis group-organisms (Bfg) or Escherichia coli (Esch. coli), and pro- and anti-inflammatory cytokines (IL-10, IL-4, IL-6, IFN-γ, TNF-α) were measured in the culture supernatant. CD4+ T-lymphocyte activation was determined by measurement of intracellular ATP following lysis of the cells. The activational response of CD4+ T-lymphocytes towards isolated and heat-inactivated intestinal organisms was increased after the probiotic treatment. Additionally, TNF-α, IL-6 and in part IFN-γ cytokine secretion by PB cells following stimulation with whole stool preparations and single members of the flora was significantly decreased, whereas the IL-10 and in part IL-4 cytokine secretion was increased at the end of the study. In contrast, the activational response of CD4+ T-lymphocytes following stimulation with whole ‘non-self’ intestinal flora was higher than by ‘self’ intestinal flora, but both responses showed a trend towards a reduction at the end of the study. This study documents a direct effect by Lb. GG on the cellular immune system of healthy volunteers and offers a promising tool to investigate systemic immunomodulation due to oral administration of probiotic microorganisms.

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Th-1-Type Cytotoxic CD8+ T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys

Journal of Virology ◽

10.1128/jvi.80.6.2771-2783.2006 ◽

2006 ◽

Vol 80 (6) ◽

pp. 2771-2783 ◽

Cited By ~ 50

Author(s):

Zichun Wang ◽

Benjamin Metcalf ◽

Ruy M. Ribeiro ◽

Harold McClure ◽

Amitinder Kaur

Keyword(s):

T Lymphocytes ◽

Immune Responses ◽

Rhesus Macaques ◽

Elispot Response ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Sooty Mangabeys ◽

Siv Infection ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Sooty mangabeys are a natural host of simian immunodeficiency virus (SIV) that remain asymptomatic and do not exhibit increased immune activation or increased T-lymphocyte turnover despite sustained high levels of SIV viremia. In this study we asked whether an altered immune response to SIV contributes to the lack of immunopathology in sooty mangabeys as opposed to species with pathogenic lentivirus infection. SIV-specific cellular immune responses were investigated in a cohort of 25 sooty mangabeys with natural SIV infection. Gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses targeting a median of four SIV proteins were detected in all 25 mangabeys and were comparable in magnitude to those of 13 rhesus macaques infected with SIVmac251 for more than 6 months. As with rhesus macaques, Th2 ELISPOT responses to SIV were absent or >10-fold lower than the IFN-γ ELISPOT response to the same SIV protein. The SIV-specific ELISPOT response was predominantly mediated by CD8+ T lymphocytes; the frequency of circulating SIV-specific CD8+ T lymphocytes ranged between 0.11% and 3.26% in 13 mangabeys. Functionally, the SIV-specific CD8+ T lymphocytes were cytotoxic; secreted IFN-γ, tumor necrosis factor alpha, and macrophage inflammatory protein 1β; and had an activated effector phenotype. Although there was a trend toward higher frequencies of SIV-specific CD8+ T lymphocytes in mangabeys with lower viral loads, a significant inverse correlation between SIV viremia and SIV-specific cellular immunity was not detected. The consistent detection of Th1-type SIV-specific cellular immune responses in naturally infected sooty mangabeys suggests that immune attenuation is neither a feature of nor a requirement for maintenance of nonpathogenic SIV infection in its natural host.

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Comparative analysis of cellular immune responses in conventional and SPF Baboons (Papio spp.)

10.1101/455881 ◽

2018 ◽

Author(s):

Elizabeth R Magden ◽

Bharti P. Nehete ◽

Sriram Chitta ◽

Lawrence E. Williams ◽

Joe H Simmons ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Lymphocyte Subsets ◽

Effector Memory ◽

Peripheral Blood Mononuclear ◽

Phenotypic Differences ◽

Successful Model ◽

Specific Pathogen ◽

Ifn Γ ◽

Cellular Immune

AbstractBaboons (papio spp.) have served as a successful model of human disease such as cardiac and respiratory, infectious, diabetes, genetics, immunology, aging, and xenotransplantation. The development of an immunologically defined specific-pathogen free (SPF) baboon model has further advanced research, especially with studies involving the immune system and immunosuppression. In this study, we compare normal immunological changes of peripheral blood mononuclear cell (PBMC) subsets, and their function in age-matched conventional and SPF baboons. Our results demonstrate that both groups have comparable numbers of different lymphocyte subsets, but there are phenotypic differences in central and effector memory T cells subsets that are more pronounced in the CD4+ T cells. Despite equal proportions of CD3+ T cells among the conventional and SPF baboon groups, PBMC show higher proliferative responses to mitogens PHA and PWM and higher IFN-γ producing cells to Con A and PWM in the conventional group. Plasma levels of the inflammatory cytokine TNF-α were significantly higher in SPF baboons. Exposure of PBMC from conventional baboons to various Toll like ligands (TLR ligands) TLR-3, TLR-4 and TLR-8 show higher IFN-γ producing cells while PBMC from SPF baboons stimulated with TLR-5 and TLR-6 ligand show higher IFN-γ producing cells. These findings suggest that while the lymphocyte subsets in conventional and SPF baboons share many phenotypic and functional similarities, specific differences exist in immune function of lymphocytes which could impact the quality and quantity of innate and adaptive immune responses. These differences should be considered for better experimental outcomes, specifically in studies measuring immunological endpoints.

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Thymic Independence of Adaptive Immunity to the Intracellular Pathogen Shigella flexneri Serotype 2a

Infection and Immunity ◽

10.1128/iai.67.8.3970-3979.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 3970-3979 ◽

Cited By ~ 18

Author(s):

Sing Sing Way ◽

Alain C. Borczuk ◽

Marcia B. Goldberg

Keyword(s):

T Lymphocytes ◽

Adaptive Immunity ◽

Adoptive Transfer ◽

B Lymphocyte ◽

Shigella Flexneri ◽

Intracellular Pathogen ◽

Partial Protection ◽

Cellular Immune Responses ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Shigella flexneri is a facultative intracellular pathogen. While immunity to several intracellular pathogens is mediated by T lymphocytes, it is unknown whether cellular immune responses are important to adaptive immunity to S. flexneri. We show that vaccination with S. flexneri serotype 2a confers protection to mice that lack T lymphocytes or gamma interferon (IFN-γ), specific depletion of T lymphocytes does not alter the protection, and adoptive transfer of splenocytes from vaccinated mice does not confer protection to naive mice. In contrast, vaccination conferred no protection to mice that lack B lymphocytes and adoptive transfer of immune sera conferred partial protection to naive mice. These data demonstrate that in the mouse bronchopulmonary model, adaptive immunity to S. flexneri 2a is an antibody-mediated, B-lymphocyte-dependent process and can be generated in the absence of T lymphocytes or IFN-γ.

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Immunophenotype of the inflammatory response in the central and enteric nervous systems of cockatiels (Nymphicus hollandicus) experimentally infected with parrot bornavirus 2

Veterinary Pathology ◽

10.1177/03009858211069166 ◽

2022 ◽

pp. 030098582110691

Author(s):

Jeann Leal de Araújo ◽

Raquel R. Rech ◽

Aline Rodrigues-Hoffmann ◽

Paula R. Giaretta ◽

Cinthya Cirqueira ◽

...

Keyword(s):

Small Intestine ◽

T Lymphocytes ◽

B Lymphocytes ◽

Inflammatory Infiltrate ◽

Homogeneous Distribution ◽

Nymphicus Hollandicus ◽

Inflammatory Infiltrates ◽

Cellular Immune ◽

Proventricular Dilatation Disease ◽

The Brain

Proventricular dilatation disease is a lethal disease of psittacine birds. In this study, we characterized the local cellular immune response in the brain, proventriculus, and small intestine of 27 cockatiels ( Nymphicus hollandicus) experimentally infected with parrot bornavirus 2 (PaBV-2). Perivascular cuffs in the brain were composed of CD3+ T-lymphocytes and Iba1+ macrophages/microglia in most cockatiels (n = 26). In the ganglia of the proventriculus, CD3+ T-lymphocytes (n = 17) and Iba1+ macrophages (n = 13) prevailed. The ganglia of the small intestine had a more homogeneous distribution of these leukocytes, including PAX5+ B-lymphocytes (n = 9), CD3+ T-lymphocytes (n = 8), and Iba1+ macrophages (n = 8). Our results indicate that perivascular cuffs in the brain and the inflammatory infiltrate in the proventriculus of PaBV-2-infected cockatiels is predominately composed of T-lymphocytes, while the inflammatory infiltrates in the ganglia of the small intestine are characterized by a mixed infiltrate composed of T-lymphocytes, B-lymphocytes, and macrophages.

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CHANGES IN THE CELLULAR IMMUNE PROTECTION OF ORGANISM IN THE PROCESS OF CHRONIZATION OF EXPERIMENTAL BACTERIAL-IMMUNE PERIODONTITIS

Ukrainian Dental Almanac ◽

10.31718/2409-0255.1.2018.01 ◽

2018 ◽

pp. 5-8

Author(s):

A.Ye. Demkovych ◽

Yu.I. Bondarenko ◽

M.M. Yakymchuk

Keyword(s):

T Lymphocytes ◽

B Lymphocytes ◽

Inflammatory Reaction ◽

Inflammatory Process ◽

Immune Defense ◽

Male Rats ◽

Natural Killers ◽

Late Period ◽

T Suppressors ◽

Cellular Immune

One of the important factors that leads to damage of structures of the periodontal complex and leads to the formation of inflammatory process of varying degrees is the disruption of immunological processes. The aim of the study was to clarify the pathogenetic role of cellular adaptive immunity in the process of formation of chronic inflammatory reaction in the late period of the experimental bacterial-immune periodontitis. The study was conducted on white, non-breeding, clinically healthy male rats. Experimental bacterial-immune periodontitis in experimental animals was caused by insertion into the tissues of the periodontal complex a mixture of microorganisms diluted with egg protein. The obtained digital data was statistically processed using parametric and nonparametric statistical methods. The article represents the results of research on the parameters of cellular immune defense, determined by the relative number of CD3+ (common T-lymphocytes), CD4+ (T-helpers), CD8+ (cytotoxic cells, T-killers), CD19+ (B-lymphocytes), CD16+ (natural killers, NK-cell) and immunoregulatory index (CD4+ / CD8+) in intact animals and on the 30th day of experimental bacterial-immune periodontitis development. It was established that the nature of the course of experimental inflammation in the tissues of the periodontal complex depended on changes in the cellular immune status, accompanied by a decrease of the content of common mature T-lymphocytes (CD3+) in the blood of animals with experimental bacterial-immune periodontitis on the 30th day of the study. In the process of the development of the experimental bacterial-immune periodontitis there was a decrease of the content of T-lymphocytes-helper (CD4+) in the blood of animals and on the 30th day of the study an increase in T-suppressors (CD8+), an increase in the content of natural killers (CD16+) and a decrease in the relative content of B-lymphocytes (CD19+). The immunoregulatory index (CD4+ / СD8+) decreased in comparison with this indicator of a group of intact animals. In rats with bacterial-immune periodontitis, an immunosuppressive state developed in the late period of the inflammatory reaction due to both T-helper cells and cytotoxic T-suppressors / killers. These changes can be considered as signs of formation of the chronic course of the inflammatory process in the tissues of periodontal complex.

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Interleukin-13, Interleukin-10, Interferon-gamma and IDO Production in Response to Home Dust Mites in Allergic Asthma

The Indonesian Biomedical Journal ◽

10.18585/inabj.v11i2.714 ◽

2019 ◽

Vol 11 (2) ◽

pp. 194-9

Author(s):

Cityta Putri Kwarta ◽

Heri Wibowo ◽

Yordan Khaedir ◽

Iris Rengganis ◽

Hanny Siti Nuraeni

Keyword(s):

Allergic Asthma ◽

Interleukin 10 ◽

House Dust Mites ◽

Atopic Asthma ◽

Assay Method ◽

Dust Mites ◽

Interleukin 13 ◽

Ifn Γ ◽

Cellular Immune

BACKGROUND: Allergic asthma is a degenerative atopic disease caused by allergic or hypersensitivity type-1. More than 50% of people with allergic asthma are caused by the presence of house dust mites (HDMs) allergens.METHODS: The cellular immunity response was evaluated through a peripheral blood mononuclear cell (PBMC) culture isolated from blood, using the ficoll gradient technique. Subjects were atopic asthma groups and non-atopic asthma groups. PBMC from each subject cultured was stimulated with HDMs allergen, then incubated in a CO2 5% incubator, 37o C for 72 hours. With the multiplex assay method, interferon (IFN)-γ, interleukin (IL)-13 and IL-10 were measured, meanwhile indoleamine 2,3-dioxygenase level (IDO) was measured by the enzyme-linked immunosorbent assay (ELISA) sandwich methods.RESULTS: The IFN-γ production in the supernatant of PBMC cultures was stimulated by phytohemagglutinin (PHA), Roswell Park Memorial Institute (RPMI) medium and allergens. The IFN-γ production in allergen-stimulated supernatants showed higher level of IFN-γ in the nonatopic group (4,681,455±3,434,851) than atopic group (4,363,300±2,067,941) even though it was not statistically significant (p=0.078). There were no differences between the mean of IL-13 production in atopic asthma group and non-atopic group. The IL-10 production in allergenstimulated supernatants was shown to be higher in nonatopic group and were statistically significantly different (p=0.015). The IDO production in allergen-stimulated supernatants was shown to be higher in the non-atopic group (272,231±269,564) than in the actopic group (13,273±400), and it was significantly different (p=0.007).CONCLUSION: Cellular immune profile of subjects with allergic asthma to Dermatophagoides pterronyssinus (Der p) is characterized by a type-2 inflammatory response that is dominant compared to type-1 inflammation (higher IL-13 ratio compared to IFN-γ) and to the role of anti-inflammation (higher IL-13 ratio compared to IL-10). The decline in IDO production in allergic asthma subjects to Der p is thought to be related to the low cellular immune response in expressing IFN-γ compared to IL-13.KEYWORDS: interleukin-13, interleukin-10, IDO, PBMC, asthma

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