scholarly journals Deviations in populations of peripheral blood mononuclear cells and endometrial macrophages in the cow during pregnancy

Reproduction ◽  
2008 ◽  
Vol 136 (4) ◽  
pp. 481-490 ◽  
Author(s):  
Lilian J Oliveira ◽  
P J Hansen
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Lower Percentage ◽  
Peripheral Blood Mononuclear ◽  
Γδt Cells ◽  
Γδt Cell ◽  
Pregnancy Status ◽  
Leukocyte Populations ◽  
Number Of Cells

The presence of conceptus alloantigens necessitates changes in maternal immune function. Here, we used the cow to evaluate whether species with epitheliochorial placentation have changes in specific leukocyte populations during pregnancy similar to those reported in species with hemotropic placentae. At days 33–34 of pregnancy, there was no effect of pregnancy status on the number of cells positive for CD8, CD4, γδT cell receptor, or the monocyte marker CD68 in the peripheral blood mononuclear cell (PBMC) population. There was, however, an increase in the proportion of CD4+cells that were positive for CD25. There was no effect of status on the proportion of PBMCs that were CD8+when comparing preparturient cows to nonpregnant cows. However, preparturient cows had an increased percentage of PBMCs that were γδT cells and CD4+CD25+and a tendency for a lower percentage that were CD68+cells. Using immunolocalization with anti-CD68, it was found that pregnant cows had increased numbers of CD68+cells in the endometrial stroma as early as days 54–100 of gestation; this increase persisted through the last time examined (day 240 of gestation). Cells positive for CD68 were also positive for another macrophage/monocyte marker, CD14. In conclusion, pregnancy in the cow is associated with changes in peripheral and endometrial leukocyte numbers, which are similar to patterns observed in other species.

scholarly journals IMMU-18. IMMUNOGENOMIC RESPONDER PHENOTYPE FROM A PHASE I TRIAL OF ANTI-LAG3 OR ANTI-CD137 ALONE AND IN COMBINATION WITH ANTI-PD-1 IN PATIENTS WITH RECURRENT GBM

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi122-vi123
Author(s):  
Christina Jackson ◽  
John Choi ◽  
JiaJia Zhang ◽  
Anna Piotrowski ◽  
Tobias Walbert ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Lower Percentage ◽  
Radiographic Evaluation ◽  
Peripheral Blood Mononuclear ◽  
Initial Resection

Abstract BACKGROUND Immune checkpoint inhibitors (ICIs) are not uniformly effective in glioblastoma treatment. Immunogenomic determinants may identify patients who are most likely to benefit from these therapies. Therefore, we compared the immunogenomic phenotype of a responder to combination anti-LAG-3 and anti-PD-1 therapy to non-responders. METHODS We performed T cell receptor (TCR) sequencing and gene expression analysis on pre-treatment, post-chemoradiation, and post-immunotherapy tumor specimens of glioblastoma patients treated with anti-LAG3 in combination with anti-PD-1 after first recurrence (NCT02658981, ongoing). We evaluated T cell clonotypes and immunophenotype of serially collected peripheral blood mononuclear cells (PBMCs) during treatment using multi-parametric flow cytometry. RESULTS To date, six patients have been enrolled in the initial anti-LAG-3 and anti-PD-1 cohort. One patient demonstrated complete response, one had stable disease, and four had progressive disease by radiographic evaluation. The responder demonstrated substantially higher TCR clonality in the resected tumor at initial diagnosis compared to non-responders (mean 0.028 vs. 0.005). Shared tumor infiltrating clonotypes with pre-immunotherapy PBMCs exhibited an increase in frequency from initial resection (6.8%) to resection at recurrence (20%). The responder’s tumor at initial resection exhibited increased gene signatures of PD1low CD8+ T cells, chemokine signaling, and interferon gamma pathways. On PBMC phenotypic analysis, the responder demonstrated significantly higher percentages of CD137+ CD8+T cells (median 8.38% vs 3.24%, p=0.02) and lower percentages of Foxp3+CD137+ CD4+T cells compared to non-responders (median 18.5% vs. 38.5%, p=0.006). Interestingly, dynamic analysis of PBMCs showed that the responder demonstrated a lower percentage of PD1+ CD8+ T cells pre-immunotherapy (median 2.5% vs.12.4%, p=0.002), with persistent decrease over the course of treatment while non-responders showed no consistent pattern. CONCLUSION Our preliminary results demonstrate significant differences in tumor and peripheral blood immunogenomic characteristics between responder and non-responders to anti-LAG3 and anti-PD-1 therapy. These immunogenomic characteristics may help stratify patients’ response to combination ICIs.

T-cell receptor V-gene usage in neoplasms of the central nervous system

1993 ◽  
Vol 78 (4) ◽  
pp. 630-637 ◽  
Author(s):  
Adrian Merlo ◽  
Luis Filgueira ◽  
Markus Zuber ◽  
Antonio Juretic ◽  
Felix Harder ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Receptor ◽  
Gene Products ◽  
Peripheral Blood Mononuclear ◽  
Infiltrating Lymphocytes

✓ The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization. Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells. Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin-2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells. Autologous peripheral blood mononuclear cells from the same patients were similarly cultured. After 4 to 5 weeks of culture, 97.3% ± 2.6% (mean ± standard deviation) of the resulting cell populations were CD3-positive lymphocytes. The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-α 2, V-β 5, 6, 8, and 12, V-γ 4 and 9 families, and from two subfamilies of V-δ 2. Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1%. In contrast, a different expression of individual V-gene products, concerning both α/β and γ/δ T-cell receptors, could be detected between cultured tumor-infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients. In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-β T-cell receptors. Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells.

scholarly journals Identification of a Committed T Cell Precursor Population in Adult Human Peripheral Blood

1997 ◽  
Vol 185 (5) ◽  
pp. 875-884 ◽  
Author(s):  
Ludovica Bruno ◽  
Pieter Res ◽  
Mark Dessing ◽  
Marina Cella ◽  
Hergen Spits
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Receptor ◽  
Surface Expression ◽  
Peripheral Blood Mononuclear ◽  
Adult Human ◽  
Rag 1

Here, we report data concerning the discovery in adult human peripheral blood of a precursor cell population able to differentiate into CD4+CD3+αβ+ mature T cells. These cells, which represent 0.1–0.5% of total peripheral blood mononuclear cells (PBMC), express substantial levels of CD4, but lack CD3 surface expression. At a molecular level, they express the pre-T cell receptor α (pTα) gene, CD3-γ, CD-δ and CD-ε, and RAG-1 recombination enzyme and have initiated rearrangements in the T cell receptor (TCR)-β locus (D–J). Moreover, low levels of CD3ε protein, but not of TCR-β chain, can be detected in their cytoplasm. Our results suggest that CD4+CD3− cells identified in peripheral blood are different from CD3−CD4+CD8− thymocytes and may contain precursors of an extrathymic T cell differentiation pathway.

T Cell Receptor Excision Circles (TRECs) Decrease in Patients after Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5357-5357
Author(s):  
Xin Du ◽  
Yangqiu Li ◽  
Shuxia Geng ◽  
Jianyu Weng ◽  
Zesheng Lu ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Peripheral Blood Mononuclear ◽  
Normal Individuals

Abstract Human thymus is required for establishment of a T-cell pool in fetal life, T-cell emigration from thymus (thymic recent emigrants [TRECs]) is a continuous thymic-dependent process. To analyze the content of signal joint Tcell receptor excision DNA circles signal joint T cell receptor excision DNA circles(sjTRECs) within peripheral blood mononuclear cells (PBMCs), thereby to infer the level of naive T cells and the recent thymic output function in patients with allogeneic stem cell transplantation. We used real-time polymerase chain reaction (PCR) to quantify SjTRECs in 5 patients with chronic myeloid leukemia-chronic phase. Five patients(4 males, 1 females; median age 37 years,) who underwent HLA-matching sibling BMT and/or peripheral blood stem cell transplantation (PBSCT) at our department. Quantitative detection of sjTRECs in DNA of peripheral blood mononuclear cells from 13 normal individuals. The median value of sjTRECs copies P1 000 PBMCs was 4.37±3.64 in normal individuals whereas it was 0.57±0.51 copies P1 000 PBMCs in patients at least two years after allogeneic stem cell transplantation (P < 0. 03). We conclude that these Patients decrease in recent thymic output function,. Therefore, measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution after transplantation.

Sign in / Sign up

Export Citation Format

Share Document