F1 ANTI-PARENT CELL-MEDIATED LYMPHOLYSIS: AUTOREACTIVE EFFECTORS AND REQUIREMENT OF PARENTAL T CELLS FOR STIMULATION

The experiments presented herein demonstrate that F1-parent T-B cell cooperation in vivo is significantly diminished by the addition of lymphoid cells of opposite parental type. This inhibition phenomenon is not a straightforward allosuppression mechanism as (a) it can be induced by parental lymphoid cells depleted by T cells, (b) it does not operate on cooperative interactions between homologous T and B cells of opposite parental type, and (c) absolutely requires the presence of F1 cells as participants in the reactions generated. The possible involvement of alloantibodies produced aberrantly under the experimental conditions employed has been ruled out by direct macrophage/antigen-presenting cell components of the reactions has been excluded. Because the presence of parental lymphoid cells only affects cooperative interactions between F1 T cells and B lymphocytes of opposite parental type but has no inhibitory effect on cooperative interactions between homologous F1, T and B cells, this (and other points discussed herein) strongly argues for the existence of one or more subsets of F1 interacting partner cells that are uniquely specific for F1, as distinct from either parental type cell interaction determinants. For reasons discussed, it appears that the most likely mechanism underlying such parental cell-induced inhibitory effects on F1-parent partner cell interactions is the development of anti-self cell interaction structure responses by F1 cells against the relevant self-specific cell-interaction structures of the parental partner cells involved.

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Tumor-Derived Exosomes (TEX) and Their Role in Immuno-Oncology

International Journal of Molecular Sciences ◽

10.3390/ijms22126234 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6234

Author(s):

Theresa Whiteside ◽

Brenda Diergaarde ◽

Chang-Sook Hong

Keyword(s):

T Cells ◽

Cancer Patients ◽

Immune Cell ◽

Parent Cell ◽

Malignant Cells ◽

Tumor Biopsy ◽

Cellular Origin ◽

Cell Functions

Extracellular vesicles (EVs) play a key role in health and disease, including cancer. Tumors produce a mix of EVs differing in size, cellular origin, biogenesis and molecular content. Small EVs (sEV) or exosomes are a subset of 30–150 nm (virus–size) vesicles originating from the multivesicular bodies (MVBs) and carrying a cargo that in its content and topography approximates that of a parent cell. Tumor-derived exosomes (TEX) present in all body fluids of cancer patients, are considered promising candidates for a liquid tumor biopsy. TEX also mediate immunoregulatory activities: they maintain a crosstalk between the tumor and various non-malignant cells, including immunocytes. Effects that EVs exert on immune cells may be immunosuppressive or immunostimulatory. Here, we review the available data for TEX interactions with immunocytes, focusing on strategies that allow isolation from plasma and separation of TEX from sEV produced by non-malignant cells. Immune effects mediated by either of the subsets can now be distinguished and measured. The approach has allowed for the comparison of molecular and functional profiles of the two sEV fractions in plasma of cancer patients. While TEX carried an excess of immunosuppressive proteins and inhibited immune cell functions in vitro and in vivo, the sEV derived from non-malignant cells, including CD3(+)T cells, were variably enriched in immunostimulatory proteins and could promote functions of immunocytes. Thus, sEV in plasma of cancer patients are heterogenous, representing a complex molecular network which is not evident in healthy donors’ plasma. Importantly, TEX appear to be able to reprogram functions of non-malignant CD3(+)T cells inducing them to produce CD3(+)sEV enriched in immunosuppressive proteins. Ratios of stimulatory/inhibitory proteins carried by TEX and by CD3(+)sEV derived from reprogrammed non-malignant cells vary broadly in patients and appear to negatively correlate with disease progression. Simultaneous capture from plasma and functional/molecular profiling of TEX and the CD3(+)sEV fractions allows for defining their role as cancer biomarkers and as monitors of cancer patients’ immune competence, respectively.

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Changes Occur in Plasma Membrane Turnover when K562 Leukemia Cells are Induced to Differentiate

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100054042 ◽

1982 ◽

Vol 40 ◽

pp. 286-287

Author(s):

L. M. Marshall

Keyword(s):

Plasma Membrane ◽

Membrane Proteins ◽

Intracellular Transport ◽

Parent Cell ◽

Membrane Turnover ◽

Coated Pits ◽

Surface Distribution ◽

Specific Proteins ◽

Erythroleukemic Cell ◽

Specific Membrane

A human erythroleukemic cell line, metabolically blocked in a late stage of erythropoiesis, becomes capable of differentiation along the normal pathway when grown in the presence of hemin. This process is characterized by hemoglobin synthesis followed by rearrangement of the plasma membrane proteins and culminates in asymmetrical cytokinesis in the absence of nuclear division. A reticulocyte-like cell buds from the nucleus-containing parent cell after erythrocyte specific membrane proteins have been sequestered into its membrane. In this process the parent cell faces two obstacles. First, to organize its erythrocyte specific proteins at one pole of the cell for inclusion in the reticulocyte; second, to reduce or abolish membrane protein turnover since hemoglobin is virtually the only protein being synthesized at this stage. A means of achieving redistribution and cessation of turnover could involve movement of membrane proteins by a directional lipid flow. Generation of a lipid flow towards one pole and accumulation of erythrocyte-specific membrane proteins could be achieved by clathrin coated pits which are implicated in membrane endocytosis, intracellular transport and turnover. In non-differentiating cells, membrane proteins are turned over and are random in surface distribution. If, however, the erythrocyte specific proteins in differentiating cells were excluded from endocytosing coated pits, not only would their turnover cease, but they would also tend to drift towards and collect at the site of endocytosis. This hypothesis requires that different protein species are endocytosed by the coated vesicles in non-differentiating than by differentiating cells.

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