Distribution Pattern Of Lymphocytes Research Articles

Carcinoma medular de mama. Caracterización de una serie de casos, 2010-2019

IntroductionMedullary carcinoma of the breast is a rare subtype of invasive carcinoma that accounts for about 3-5% of all cases of breast cancer. The aim of this study was to characterize a series of cases with anatomopathological diagnosis of medullary carcinoma of the mother, from Hospital Clínico Quirúrgico Docente Joaquín Albarrán, in the period 2010 to 2019. MethodA retrospective, descriptive and observational study was conducted, in which the biopsy records were reviewed, collecting variables such as age and macroscopic and histological characteristics. ResultsIn the period from 2010 to 2019, the histopathological diagnosis of 9 cases of medullary carcinoma of the breast was made, of which 77.8% were typical medullary carcinoma of the breast and 22.2%, atypical. Only 33.3% of the lesions presented intratumoral necrosis; lymphatic permeation was present in 100% of cases; lymph node metastasis was confirmed in 33.3% of cases; The immunohistochemical study revealed that 88.9% of the tumors did not express hormonal and Her-2 receptors, so they were classified as triple negative or basal molecular subtype. ConclusionFor the histopathological diagnosis of CMM, the presence of lymphoplasmocytic infiltrate is essential, always detecting the intensity and distribution pattern of lymphocytes and plasma cells in relation to the characteristics of tumor cells (individual disposition and characteristics). The triple negative molecular subtype was the most frequent.

EPA-0050 - Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: Further evidence for disease course-related immune alterations?

Based on the neuroinflammatory hypothesis of schizophrenia, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher lymphocyte densities were observed in residual schizophrenia. In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia. BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.

Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: Further evidence for disease course-related immune alterations?

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain's mononuclear phagocyte system (microglial cells) is activated during acute psychosis. Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P=0.047, right: P=0.038; CD20: left: P=0.020, right: P=0.010) and controls (CD3: left: P=0.057, right: P=0.069; CD20: left: P=0.008, right: P=0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P=0.030, right: P=0.012). A similar trend emerged when this group was compared to controls (left: P=0.090, right: P=0.090). BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.

Flow cytometric characterization of tumor-associated macrophages in experimental gliomas.

Although microglia have been suggested to be a component of the inflammatory reaction to tumors of the central nervous system, their role in glioma biology remains unknown. One obstacle to studying the function of microglia is the inability to effectively separate them from macrophages. Because flow cytometry can effectively discern immune cells with similar surface antigens, we evaluated its role in characterizing the mononuclear cell infiltration in experimental gliomas. Freshly prepared rat C6, 9L, and RG-2 tumor specimens were labeled ex vivo with monoclonal antibodies against CD11b/c, CD45, and CD8a antigens and analyzed by flow cytometry. The extent of microglia (CD11b/c(high), CD45(low)), macrophage (CD11b/c(high), CD45(high)), and lymphocyte (CD11b/c(negative), CD45(high)) infiltration into tumors, tumor periphery, and contralateral tumor-free hemispheres was measured for each glioma type. Microglia, which accounted for 13 to 34% of viable cells, were distributed throughout the central nervous system and were present in the tumors, tumor periphery, and contralateral tumor-free hemispheres. In contrast, macrophages were less prominent within the tumors and tumor periphery (4.2-12%) and were scarce in the contralateral tumor-free hemispheres (0.9-1.1%). Among the tumor types, RG-2 gliomas had the least microglia/macrophage infiltration. The frequency and the distribution pattern of lymphocytes also varied among tumor models. Whereas lymphocytes accounted for more than one-third of the cells in C6 and 9L tumors, they represented only 1% of cells in RG-2 gliomas. More abundant than macrophages and scattered throughout the central nervous system, microglia account for a significant component of the inflammatory response to experimental gliomas. A better understanding of microglial function in gliomas may be important in the development of immunotherapy strategies.

小児および若年成人のか粒リンパ球についての研究

In this study, we investigate the percentage and absolute number of granular lymphocytes (GL) in venous blood smears and the percentage of CD16+ and CD57+ lymphocytes in the peripheral venous blood of 91 healthy controls (1 to 29 years old) and 168 patients with various diseases (1 month to 36 years old). GL were morphologically classified into four subsets: large-sized lymphocytes with large granules (LL-LG), large-sized lymphocytes with small granules (LL-SG), medium-sized lymphocytes with large granules (ML-LG) and medium-sized lymphocytes with small granules (ML-SG). The results were as follows: 1) In the controls, the percentage of GL in total lymphocytes was 10.0 +/- 6.2% (mean +/- 1SD). Therefore its normal value was below 22.4% (mean +/- 2SD). The absolute count of GL was 320.7 +/- 221.0/mm3. The percentages of LL-LG, LL-SG, ML-LG and ML-SG in total lymphocytes were 1.7 +/- 2.2%, 2.3 +/- 2.8%, 2.6 +/- 2.3% and 3.4 +/- 2.7%, respectively. 2) In flow cytometric studies, the percentage of CD16+ in the controls was 10.2 +/- 6.7%; CD57+, 8.2 +/- 5.1%; CD57+ CD16+, 4.2 +/- 3.3%; CD57+ CD16-, 4.0 +/- 2.8%; CD57- CD16+, 6.4 +/- 4.8%. The distribution patterns of lymphocytes by two-color analysis with FITC-labelled anti-CD16 and PE-labelled anti-CD57 monoclonal antibodies in the controls were classified into four groups. 3) Only seven of the 168 patients exhibited significantly high percentage of GL in total lymphocytes. They consisted of 4 splenectomized patients and 3 patients with pancytopenia, two of whom had pancytopenia complicated by immunoglobulin deficiency. Five of the 7 patients also had markedly high percentage of CD16+ and/or CD57+ lymphocytes. In these 5 patients, the ratios of four subsets of GL and the distribution patterns of lymphocytes with CD16 and CD57 surface antigens were different from the patient to patient and those for controls.

Interaction of human lymphocytes with fluid phase human C3b detected by immunofluorescence

Human lymphocytes obtained from tonsils and peripheral blood were found to bind human fluid phase C3b, obtained by trypsin treatment. This binding was detected by indirect immunofluorescence (IIF) using specific anti-C3 antisera. Lymphocytes isolated from thymus tissue scored low percentages in IIF, indicating that the main population of thymus-derived lymphocytes are T cells. The distribution pattern of C3b-binding cells was compared with that of cells forming rosettes with sheep erythrocytes coated with antibody and complement (EAC) and with sheep erythrocytes (E) only, as well as with that of Ig-bearing lymphocytes, as detected by direct immunofluorescence. It appeared that the distribution pattern of lymphocytes which can bind fluid phase C3b is similar to that of EAC rosette-forming and of Ig-bearing lymphocytes. Pre-incubation of the lymphocytes with C3b and pretreatment of the cells with trypsin decreased the capacity to form rosettes and to bind C3b to their surface. Human monocytes granulocytes and erythrocytes did not bind fluid phase C3b, as judged by IIF. Therefore, the selective binding of fluid phase C3b to lymphocytes provides a specific method for the detection of complement-reactive lymphocytes in lymphoid cell preparations.

Lymphocyte surface receptors and leukemia virus-induced immunosuppression.

The number and distribution patterns of lymphocytes in the spleens and lymph nodes of Balb/c mice which express immunoglobulin surface receptors were studied in terms of the effects of a murine leukemia virus on the immune-response mechanism. Friend leukemia virus induces a prompt, marked depression of the immune response of mice to antigens such as sheep erythrocytes and E. coli LPS. A functioning T- and B-lymphocyte system is necessary for the response to the SRBC's whereas E. coli LPS, a T cell-independent antigen, stimulates B cells alone. Although the responses to both classes of antigen were markedly depressed in FLV-infected mice, the major defect appeared to be impairment of B-cell function, at least early in the course of infection. In order to examine in more detail the mechanism of interaction between FLV and lymphoid cells with Ig surface receptors, presumably B cells, immmunofluorescent analyses were performed with spleen, and lymph node cells from FLV-infected mice. Within a few days after infection there was a marked decrease in the percentage of spleen cells with Ig surface molecules, although the absolute number of these cells was either unchanged or increased due to marked splenomegaly caused by the virus. A marked decrease in the percentage of splenocytes with theta antigen, considered a marker for mature T cells, also was evident in infected mice. The number of spleen cells showing evidence of FLV infection (i.e., positive for FLV-associated antigens) increased rapidly during the first few days after infection, and within 2 to 2 1/2 weeks nearly all of the nucleated splenocytes were positive for the tumor antigen. In contrast to the results for spleen cells, there were increases rather than decreases in the percentages of Ig-positive and theta-positive cells in the lymph nodes after infection. The number of lymph-node cells that showed the presence of FLV antigen was much lower than in the spleen, and their appearance was also much slower as the leukemic process progressed. Despite these differences between spleen and lymph-node cells in terms of relative percentages of Ig- and theta-positive lymphocytes, relatively similar depressions were evident for the percentages of lymphoid cells that could redistribute their surface Ig receptors into polar caps when incubated with anti-Ig serum at 37 C. Marked impairment of the Ig-capping responses for both spleen and lymph-node cells paralleled the course of infection and development of immunosuppression. These observations indicate that murine leukemia virus infection can both alter the responsiveness of immunocompetent cells to T-dependent and independent antigens and depress the number and normal functional activity of these cells, as reflected by altered surface Ig receptors and antigens.

The distribution of 51Cr-labeled lymphocytes into antigen-stimulated mice. Lymphocyte trapping.

The localization of syngeneic (51)Cr-labeled lymph node cells was investigated in CBA/J mice previously challenged with sheep erythrocytes, Salmonella H antigen, keyhole limpet hemocyanin, C57BL/6J skin, or rat skin. The effect of time, dose, and route of antigen administration on lymphocyte migration was studied in both primary and secondary responses. When the distribution pattern of lymphocytes was examined after 20-24 hr, it was found that increased localization of labeled cells occurred in spleen after intravenous or intraperitoneal antigen injection, and in draining lymph nodes after subcutaneous antigen injection or skin grafting. Increased localization (trapping) of lymphocytes was antigen dose dependent and could be demonstrated when 1-6 hr had elapsed between intravenous antigen administration, or when 24 hr had elapsed between subcutaneous antigen administration and intravenous cell infusion. Trapping was transient, lasting approximately 24 hr. Maximal trapping of lymphocytes in the draining nodes occurred 9 days after skin grafting in the first-set allograft response, and 3 days after grafting in the second-set allograft and first-set xenograft responses. The cell type trapped, the specificity and mechanism of action of the trap, and the role of lymphocyte trapping in the initiation of immune responses are discussed.