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PubMedDate not supplied

Chronic exposure to low doses of lead results in renal infiltration of immune cells, NF-kappaB activation, and overexpression of tubulointerstitial angiotensin II.

Chronic exposure to low doses of lead results in generation of reactive oxygen species, reduced nitric oxide availability, and arterial hypertension. The present studies were done to define if other conditions associated with oxidative stress, such as renal interstitial inflammation, nuclear factor-kappaB (NF-kappaB) activation, and cells expressing angiotensin II, are, in fact, features of low-dose lead exposure. Male Sprague-Dawley rats were randomly assigned to the lead group (n = 8) or the control group (n = 9). The lead group received 100 ppm lead acetate in the drinking water for 14 weeks. At the end of this period of time, rats were killed under general anesthesia, and the kidneys were harvested for studies. The lead-exposed group presented focal tubulointerstitial damage and highly significant increments in nitrotyrosine immune staining, lymphocyte and macrophage infiltration, angiotensin II-positive cells, and intranuclear positive staining for the p65 DNA-binding subunit of NF-kappaB in tubulointerstitial cells. Tubulointerstitial inflammation, cells expressing angiotensin II, and NF-kappaB activation are consequences of a 3-month low-dose exposure to lead and likely play a role in the development of hypertension and chronic lead nephropathy.

Angiotensin II↗

PubMed2026

Effect of Tertiary Lymphoid Structures on Immune Cell Infiltration in the Tumor Microenvironment and Prognosis in Lung Adenocarcinoma.

Tertiary lymphoid structures (TLSs) modulate immune responses in various solid tumors, but their comprehensive role in lung adenocarcinoma (LUAD) remains unclear. In this study, we analyzed RNA-seq data from 539 LUAD patients in The Cancer Genome Atlas (TCGA) and microarray data from 223 samples from the Gene Expression Omnibus (GEO, GSE13213, and GSE37745). TLS signatures were evaluated via unsupervised consensus clustering based on 12 chemokine transcriptome signatures. The relationships between TLS and clinical characteristics, tumor microenvironment (TME) cell infiltration, and prognosis were assessed using ESTIMATE and CIBERSORT. A prognostic model was established using LASSO regression and validated with external datasets. Additionally, H&E and IHC analyses were performed to explore associations between intratumoral TLS density, immune-related molecular expression, and patient prognosis in LUAD. Consensus clustering of the TCGA cohort revealed two distinct LUAD patient clusters according to TLS abundance. Cluster 1 exhibited greater immune cell infiltration, more favorable prognosis, and increased expression of immune checkpoint molecules. We developed a prognostic model comprising eight survival-associated genes that act as independent prognostic factors for patient survival. H&E/IHC analyses revealed that TLS density-regardless of pathological stage-was associated with better prognosis; higher intratumoral TLS density/proportion was also related to more favorable outcomes. IHC confirmed that survival-associated genes (CD5, HLA-DMB, and P2RY13) are independent prognostic indicators in LUAD. Our study demonstrated the close relationship between TLS signatures and an active immune microenvironment, highlighting their potential as independent prognostic indicators in LUAD.

Humans↗

PubMed1995

[Identification and analysis of immune cells infiltrating into the glomerulus and interstitium in lupus nephritis].

This study was performed to investigate the role of cell-mediated immunity in lupus nephritis (LN). Frozen sections from 38 patients with LN were examined by indirect immunoalkaline-phosphatase labeling using monoclonal antibodies to identify the immune cells infiltrating into the interstitium and glomerulus. 14 patients showed minor glomerular abnormality (MGA), 9 had mesangial LN (MesLN), 12 had diffuse proliferative LN (DPLN) and 3 had membranous LN (MLN). Monocyte/macrophage and helper/inducer T cells infiltrated in the interstitium predominantly, but intraglomerular infiltration of these cells was rare. Monocyte/macrophage and suppressor/cytotoxic T cell levels were significantly higher (p < 0.05) in the interstitium in DPLN patients and monocyte/macrophage level was significantly higher (p < 0.05) in MesLN patients than in MGA patients. In the interstitium, serum creatinine level was highly correlated with infiltrations of suppressor/cytotoxic T cell, monocyte/macrophage (p < 0.01), pan T cell and total leucocyte (p < 0.05). Clinical activity score was correlated with suppressor/cytotoxic T cell (p < 0.001), monocyte/macrophage and pan T cell (p < 0.01). These results suggest that suppressor/cytotoxic T cell and and monocyte/macrophage may play an important role in the progression of lupus nephritis.

Antibodies, Monoclonal↗

PubMed1994

Intraglomerular immune cell infiltration and complement 3 deposits in membranoproliferative glomerulonephritis type I: a serial-biopsy study of 25 cases.

We examined chronological changes in intraglomerular immune cell infiltration in comparison to the changes in glomerular complement 3 (C3) deposits (C3-D) and serum complement levels in 25 patients with membranoproliferative glomerulonephritis (MPGN) type I. These patients were divided into the following two groups: group A (n = 13), cases in which there were fewer intraglomerular C3-D at the second biopsy (2nd-Bx) than at the first biopsy (1st-Bx); and group B (n = 12), those in which the amount of C3-D at the 2nd-Bx was greater than or equal to that at the 1st-Bx. At the 1st-Bx, monocytes (Mo)/macrophages (M phi) and total leukocytes (TLC) were the predominant cell types in both groups, whereas T cells were less marked. At the 2nd-Bx, only group A showed a significant decrease in the number of either Mo/M phi (P < 0.01), TLC (P < 0.01), pan-T cells (P < 0.01), or intraglomerular nuclei per glomerular cross-section ([NIN] P < 0.01). In group B, there was a positive correlation between the number of intraglomerular pan-T cells (CD3-positive cells) and M phi (CD68-positive cells, P < 0.05 at the 1st-Bx and P < 0.01 at the 2nd-Bx), but not in group A. An improvement in light-microscopic findings and a significant decrease of urinary protein excretion (P < 0.05) at the 2nd-Bx was observed only in group A. Hypocomplementemia (hypo-C) was found in 12 of 13 cases of group A and in eight of 12 cases of group B at the 1st-Bx. Hypo-C in group A was not found at the 2nd-Bx. On the other hand, in group B, hypo-C was still observed in the eight cases and was found in one additional case at the 2nd-Bx.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2005

Adenovirus mediated CTLA4Ig gene inhibits infiltration of immune cells and cell apoptosis in rats after liver transplantation.

AIM: To investigate the role of adenovirus-mediated CTLA4Ig gene therapy in inhibiting the infiltration of macrophages and CD8(+) T cells and cell apoptosis after liver transplantation. METHODS: The rat orthotopic liver transplantation model was applied. The rats were divided into three groups: group I: rejection control (SD-to-Wistar); group II: acute rejection treated with intramuscular injection of CsA 3.0 mg/(kg x d) for 12 d (SD-to-Wistar+CsA); groupIII: injection of 1 x 10(9) PFU adenovirus-mediated CTLA4Ig gene liquor in dorsal vein of penis 7 d before liver transplantation (SD-to-Wistar+CTLA4Ig). Immunohistochemistry and transferase-mediated dUTP nick-end labeling (TUNEL) were used to analyze the expression of CTLA4Ig gene in liver, infiltration of macrophages and CD8(+) T cells, cell apoptosis in grafts at different time-points after liver transplantation. Histopathological examination was done. RESULTS: CTLA4Ig gene expression was positive in liver on d 7 after administering adenovirus-mediated CTLA4Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of macrophages and CD8(+) T cells in CTLA4Ig-treated group was less than in rejection control group and CsA-treated group. The apoptotic index of rejection group on d 3, 5, and 7 were significantly higher than that of CTLA4Ig-treated group. A good correlation was found between severity of rejection reaction and infiltration of immune activator cells or cell apoptotic index in grafts. CONCLUSION: CTLA4Ig gene is constantly expressed in liver and plays an important role in inducing immune tolerance.

Abatacept↗

PubMed2026

Pan-cancer analysis identifies APOC1 as a TAM-derived modulator of adaptive immune resistance and predictor of therapeutic response.

BACKGROUND: Apolipoprotein C1 (APOC1) has been implicated in several malignancies, yet its expression patterns, clinical significance, and immunomodulatory roles across cancer types remain poorly characterized. METHODS: We performed a comprehensive multi-omic analysis of APOC1 across 33 cancer types integrating transcriptomic, proteomic, genomic, epigenomic, and pharmacogenomic data from TCGA, GTEx, CPTAC, and multiple independent external cohorts. Immune infiltration was assessed using seven complementary algorithms. Spatial transcriptomics and single-cell RNA sequencing were employed to determine the cellular source of APOC1 expression. RESULTS: APOC1 upregulation in most cancers was associated with cancer type-specific prognosis. After adjustment for clinical covariates and macrophage infiltration, high APOC1 remained an independent adverse factor in KIRC, LGG, and STAD. APOC1 expression positively correlated with genomic instability hallmarks, including homologous recombination deficiency and aneuploidy, with these associations largely independent of immune infiltration; in contrast, associations with tumor mutational burden were substantially confounded by macrophage abundance. Immune infiltration analysis revealed a pattern consistent with adaptive immune resistance: APOC1 correlated positively with immune-activating signatures (STAT1, MHC-II, TCR signaling) and immunosuppressive M2 macrophages and Tregs, yet negatively with anti-tumor effectors (activated NK cells, dendritic cells). Spatial transcriptomics and single-cell RNA sequencing identified tumor-associated macrophages (TAMs) as the primary cellular source of APOC1, with transcripts co-localizing with CD68 in tissue sections. APOC1 expression correlated with multiple immune checkpoint molecules and was elevated in responders to immune checkpoint blockade, consistent with an inflamed yet regulated tumor microenvironment. Pharmacogenomic analyses revealed that APOC1-high tumors display distinct drug response profiles, characterized by resistance to MAPK pathway inhibitors and potential sensitivity to the HDAC inhibitor Entinostat. CONCLUSION: This pan-cancer analysis establishes APOC1 as a context-dependent biomarker and a TAM-derived modulator of adaptive immune resistance, with prognostic and therapeutic implications across malignancies. APOC1-expressing TAMs represent a potential target for combination immunotherapy strategies.

APOC1↗

PubMed2000

Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+ T cells at the perilesional site.

In situ immune infiltrates in lesional, perilesional, and nonlesional skin biopsies from patients with vitiligo were analyzed by immunohistochemistry and compared with immune infiltrates found in the skin of normal healthy donors and relevant disease controls. An increased influx of activated skin-homing T cells and macrophages were seen in the perilesional biopsies. The overall percentages of cutaneous leukocyte-associated antigen-positive (CLA+) T cells were similar to those found in normal healthy donors. This is compatible with the similar expression of E-selectin. Most strikingly, however, the CLA+ T cells in perilesional skin were mainly clustered in the vicinity of disappearing melanocytes, and 60% to 66% of these interacting T cells expressed perforin and granzyme-B. The perforin+/granzyme-B+ cells were not seen in locations different from that of disappearing melanocytes. Interestingly, the majority of the infiltrating T cells were HLA-DR/CD8+. Another hallmark of the present study is the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in the epidermis at the site of interaction between the immune infiltrates and the disappearing melanocytes. The data presented in this study are consistent with a major role for skin-homing T cells in the death of melanocytes seen in vitiligo.

Adult↗

PubMed2025

Identification of mitophagy-related biomarkers with immune cell infiltration in psoriasis.

BACKGROUND: Psoriasis is an inflammatory disorder characterized by scaly erythematous plaques and significant comorbidities. Recent studies have suggested that impaired mitophagy, the cellular mechanism for removing dysfunctional mitochondria, may contribute to the pathogenesis of psoriasis. METHODS: In this study, we analyzed bulk RNA sequencing data from 167 healthy individuals and 177 patients with psoriasis obtained from the Gene Expression Omnibus database (GSE30999 and GSE54456). Mitophagy-related genes were isolated using weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed and protein-protein interaction networks were constructed for the functional enrichment of genes associated with mitophagy. The correlations between genes associated with mitophagy, signaling pathways, and immune cell infiltration were analyzed. The potential diagnostic value of genes associated with mitophagy was evaluated using receiver operating characteristic (ROC) curves, which were validated in imiquimod-induced psoriatic skin lesions in mice. RESULTS: We identified 3,839 differentially expressed genes between healthy individuals and patients with psoriasis, and 23 genes were selected as hub genes showing a high correlation with mitophagy in psoriasis. GO and KEGG analyses revealed that hub and associated genes were significantly correlated with skin functions, such as epidermal development and keratinocyte differentiation. In addition, mitophagy-related genes were negatively associated with pro-inflammatory and pro-proliferation pathways in psoriasis. Among the immune cells, CD4+ T cells were most significantly affected by mitophagy-related genes. ROC analysis demonstrated that mitophagy-related genes, especially ACER1, C1ORF68, CST6, FLG2, GJB3, GJB5, GPRIN2, KRT2, and SPRR4 were potential biomarkers of psoriasis for use in diagnosis or treatment. CONCLUSIONS: Mitophagy-related genes play crucial roles in psoriasis and have potential use as biomarkers, providing insights into disease mechanisms and therapeutic targets. Further research may lead to the development of new strategies for psoriasis management.

Psoriasis↗

PubMed1995

Low dose streptozotocin causes diabetes in severe combined immunodeficient (SCID) mice without immune cell infiltration of the pancreatic islets.

Streptozotocin (stz) given in low doses (40 mg/kg body weight) on 5 consecutive days to susceptible strains of mice causes diabetes. Previous studies have shown that the induction of diabetes is associated with inflammatory infiltrates within the pancreatic islets. However, it is unclear whether stz causes limited beta cell destruction followed by insulitis or whether the diabetogen promotes immune cell influx into the pancreatic islets, followed by immune-mediated beta-cell destruction. It is also unclear whether stz given in sub-diabetogenic doses is capable of causing diabetes independent of cell-mediated processes. Here we have examined these possibilities in CB.17 Scid mice which lack functional T and B cells but have immunocompetent macrophages and NK cells. Low dose stz given to Scid mice caused diabetes in approximately 50% of mice of both sexes by 21 days (14/24 males; 10/18 females). Sections of pancreas were examined immunohistochemically for the presence of MAC-1 positive cells (macrophages and natural killer cells) in the exocrine, peri- and intra-islet regions at different time points following the administration of stz. There were no statistically significant differences in the number of immunoreactive cells in the three locations between tissues obtained from stz-injected mice (3, 7, 14 and 21 days after stz injection and at onset of diabetes) and buffer-injected Scid mice. Although diabetic Scid mice showed a reduced number of insulin immunoreactive cells and peri- and intra-islet distributed glucagon cells, no insulitis was seen histochemically. In parallel studies, normal Swiss male mice given stz at a similar dose developed diabetes (10/10) associated with insulitis which consisted predominantly of CD4, CD8 and MAC-1 cells. Balb/c mice given stz similarly, also developed diabetes (5/8) without showing insulitis, although a moderate increase in the number of macrophages were observed within several islets. These studies demonstrate that stz administered in multiple low doses to Scid mice can cause beta cell destruction and diabetes in the absence of immune cell infiltrate within the pancreatic islets.

Animals↗

PubMed2003

The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators.

BACKGROUND: The aims of this study were to characterize, phenotypically, the immune infiltrate in human breast cancers, to assess the activation status of tumor-infiltrating lymphocytes (TIL), and to define the association of these findings with established prognostic indicators. METHODS: Immunohistochemistry was performed on frozen sections of 60 primary breast cancers by use of monoclonal antibodies to T lymphocytes (CD3), T-helper cells (CD4), cytotoxic T-cells (CD8), natural killer cells (CD56), interleukin-2 receptors (IL-2R), and major histocompatibility (MHC) class I antigen (HLA-ABC) and MHC class II antigen (HLA-DR). RESULTS: All tumors stained positive for CD3, CD4 and CD8, but with marked variation in the intensity of the infiltrate. In tumors with a moderate infiltrate of TIL, there was a trend toward a greater representation of T-helper cells. However, as the intensity of TIL increased, there was a decline in the proportion of T-helper cells and a concomitant rise in the relative proportion of cytotoxic T cells. There was a relative paucity of natural killer cells. A significant association was found between the intensity of TIL and the number of positive nodes (P=.02) and the intensity of the infiltrate of both T-helper cells and cytotoxic T cells with ER expression (P=.03 and.05, respectively). Most tumors stained positive for IL-2R. The expression of IL-2R was associated with the intensity of TIL (P<.0001), T-helper cells (P<.002), cytotoxic T cells (P=.01) and natural killer cells (P=0.04), and also with the degree of lymph node positivity (P=.02) and histologic tumor grade (P=.05). MHC class II expression was variable, and a large proportion of the tumors showed limited expression in individual cancer cells. There was an association between the expression of HLA-DR in tumor cells and the activation status of TIL (P=.03). CONCLUSION: An immune infiltrate is an invariable finding in breast cancers, and the intensity of the infiltrate is greater in node positive tumors. Additionally, TIL may well be activated, albeit partially, in most tumors, suggesting that cell-mediated immune mechanisms are functionally intact.

Breast Neoplasms↗

PubMed2025

MicroRNA-486: a dual-function biomarker for diagnosis and tumor immune microenvironment characterization in non-small cell lung cancer.

BACKGROUND: This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach. METHODS: We conducted systematic search and meta-analysis of diagnostic studies from major biomedical databases from inception through April 04, 2025, followed by comprehensive bioinformatics interrogation. Protein-protein interaction (PPI) networks were constructed using STRING to identify key hub genes regulated by miR-486. Validation of hub genes employed TCGA datasets, while immune infiltration analysis utilized TIMER2.0 platform. RESULTS: The meta-analysis indicated that miR-486, both individually and in combination, could be effective biomarkers for NSCLC detection. Afterwards, functional enrichment analyses of miR-486 target genes highlighted significant ontology terms and pathways crucial to the initiation and progression of NSCLC. PPI networks revealed key proteins and modules that participate in multiple essential pathways associated with NSCLC pathogenesis. Furthermore, the identified hub genes were validated for differential expression in cancerous versus normal tissues, suggesting their potential diagnostic utility, while subsequent survival analyses confirmed their prognostic value through significant associations with overall survival. Notably, these hub genes were found to be significantly associated with immune infiltration levels, immune microenvironment scores, and immune-related proteins in NSCLC. CONCLUSIONS: This dual-modality investigation establishes miR-486 as a multi-functional biomarker in NSCLC, demonstrating both diagnostic utility and immunoregulatory potential through tumor microenvironment modulation.

Humans↗

PubMed1999

Intraglomerular monocyte infiltration and immune deposits in diffuse lupus glomerulonephritis.

Previous studies have suggested that separately, glomerular monocyte (MO) infiltration and persistent glomerular immune deposits have opposite prognostic implications in lupus nephritis (LN). To see whether these pathological variables are inversely related, 37 renal biopsy specimens from 37 patients with diffuse proliferative LN were assessed histologically for activity index, chronicity index, and mean glomerular deposit score per biopsy (deposit index [DI]); the latter was determined semiquantitatively on a scale of 0 to 4.0. Frozen sections were double immunolabeled for immunoglobulin G (IgG) and CD68, a marker for MOs. For each glomerulus in each biopsy specimen, the number of CD68+ cells was counted and the amount of IgG scored semiquantitatively on a scale of 0 to 4.0. For each biopsy specimen, the mean number of MOs per glomerular cross-section (MO index [MOI]) was calculated. Linear regression analysis showed a moderately strong inverse correlation between individual glomerular IgG deposit score and individual glomerular MO count (r = -0.447; P < 0.0001), a weaker but significant inverse correlation between DI and MOI (r = -0.350; P = 0.0389), and a positive correlation between the DI determined histologically in each case and the corresponding DI scored on the immunolabeled sections (r = 0.534; P = 0.0105). The results indicate that the amount of glomerular deposit and the extent of glomerular MO infiltration are inversely related in LN.

Antigens, CD↗

PubMed1995

Immune cell infiltration and persistence in the mouse trigeminal ganglion after infection of the cornea with herpes simplex virus type 1.

Following inoculation of the mouse cornea with herpes simplex virus type 1 (HSV-1), the spread of virus was investigated and the types of immune cell infiltrating the trigeminal ganglion (TG) were identified in low temperature paraffin wax sections. Virus antigen was first found on day 3 and was absent after day 14. Early presentation of antigen to T cells may occur since increased expression of major histocompatibility complex (MHC) class II antigens, including de novo expression on satellite and Schwann cells, was detected in foci of such antigen on day 3. A second large peak of such expression was detected on day 10 together with increasing numbers of B and T cells. Large numbers of these lymphocytes and extensive expression of MHC class II were seen in the TG well into the phase of virus latency; the significance of this is discussed.

Animals↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗

PubMed1993

Expression of intercellular adhesion molecule-1 on transitional cell cancer. Possible significance in immunity against tumor cells.

Immunohistochemical examination demonstrated expression of intercellular adhesion molecule-1 (ICAM-1) on 17 of 44 transitional cell cancers (TCCs) but not on normal transitional cells. ICAM-1 was frequently expressed in higher stage tumors, especially in those with abundant immune cells scattered within tumor. Analysis of infiltrating immune cells showed that they were composed mainly of T lymphocytes and a smaller number of macrophages bearing the lymphocyte function-associated antigen-1 (LFA-1). Expression of ICAM-1 on transitional cell cancer cell lines was augmented by in vitro treatment with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Furthermore, Northern blot analysis revealed higher quantities of a 3.3-kb RNA in T24 cells exposed to interferon-gamma or tumor necrosis factor-alpha. These results suggest that the expression of ICAM-1 on transitional cell cancers might be modified by cytokines produced by infiltrating immune cells, which might facilitate immune responses against cancer cells.

Aged↗

PubMed1989

Infiltration of immune T cells in the brain of mice with herpes simplex virus-induced encephalitis.

Herpes simplex virus (HSV) infection of mice can induce viral encephalitis. Using two-fluorochrome immunofluorescence, our present study shows that though there is extensive myelin loss and necrosis in the brain stem of mice with HSV encephalitis, only some oligodendrocytes, astrocytes and microglial cells are infected. T cells that express CD4 or CD8 and a large number of CD4+, F4/80+ macrophages are present in perivascular infiltrates close to and in contact with HSV-infected cells in areas of massive myelin loss. These findings suggest that the resultant infiltration of immune cells into the brain during HSV-1 infection may cause as much damage as the virus itself.

Animals↗

PubMed1992

Sequential immunocytological evaluation of murine transitional cell carcinoma during intralesional bacillus Calmette-Guerin and interleukin-2 immunotherapy.

The antitumor effect of intralesionally administered recombinant interleukin-2 was highly effective (90% complete response) in murine bladder cancer. We postulated that interleukin-2 may be integral to the Bacillus Calmette-Guerin-induced antitumor response in human bladder cancer. Flow cytometric evaluation of the tumor infiltrates was compared before and after intralesional treatment of an established, untreated murine bladder tumor model with recombinant interleukin-2, Bacillus Calmette-Guerin or saline. Large increases in the number of tumor infiltrating immune cells occurred between the day of randomization and the second day (one day after the first treatment) in all three groups. However, since tumor volume was reduced by treatment, the ratios of the immune cells to tumor volume was increased. The ratios of T(helper), T(cytotoxic)/suppressor cells, macrophages, and natural killer cells to tumor volume were 1.5 to 3.4 times higher in the interleukin-2 and Bacillus Calmette-Guerin groups in comparison to the saline group. The ratio of T(helper)/T(cytotoxic)/suppressor cells however, remained approximately the same despite treatment. Over the next 22 days all subpopulations of tumor infiltrating immune cells decreased in number and frequency to less than measurable levels. The similar modulation of infiltrating immune cell subpopulations by Bacillus Calmette-Guerin and interleukin-2 may indicate that the production of interleukin-2 is part of the tumor modulating mechanism of Bacillus Calmette-Guerin.

Animals↗

PubMed2005

Hypertension induced by aortic coarctation above the renal arteries is associated with immune cell infiltration of the kidneys.

BACKGROUND: Renal tubulointerstitial infiltration of activated T cells and macrophages is invariably present and plays a role in elevation of arterial pressure in nearly all animal models of hypertension (HTN). The role, if any, of elevated renal arterial pressure in the pathogenesis of this inflammatory process is uncertain. Also unclear is whether the cellular infiltration is caused by the local activation of immune cells in the kidney or a consequence of leukocyte activation in the systemic circulation. METHODS: We studied activation of peripheral blood leukocytes and cellular infiltration in the kidneys of Sprague-Dawley rats with abdominal aorta coarctation (banding) above renal arteries, which causes severe HTN proximal but not distal to coarctation. RESULTS: Compared with the sham operated controls, the aorta-banded group exhibited tubulointerstitial accumulation of activated T cells, macrophages, angiotensin-II positive cells, leukocyte function-associated antigen-1 integrin expressing cells, increased nitrotyrosine abundance (a measure of oxidative stress), and increased macrophage chemoattractant protein-1 in the kidneys which are not exposed to HTN in this model. These findings were associated with the activation of the circulating leukocytes in the aorta-banded animals. CONCLUSIONS: Increased baromechanical stress is not a requisite for accumulation of T cells and macrophages in the kidney in the coarctation-induced HTN and possibly in other hypertensive disorders. On the contrary, renal hypoperfusion and the consequent activation of renin-angiotensin system may mediate this process by promoting local induction of chemoattractant and inflammatory cytokines. The observed tubulointerstitial inflammation in this model is associated with leukocyte activation in the systemic circulation.

Angiotensin II↗