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Summary: There have been substantial strides forward in our understanding of the contribution of regulatory T (Treg) cells to cancer immunosuppression. In this issue, we present a series of papers highlighting emerging themes on this topic relevant not only to our understanding of the fundamental biology of tumour immunosuppression but also to the design of new immunotherapeutic approaches. The substantially shared biology of CD4+ conventional T (Tconv) and Treg cells necessitates a detailed understanding of the potentially opposing functional consequences that immunotherapies will have on Treg and Tconv cells, a prominent example being the potential for Treg‐mediated hyperprogressive disease following anti‐PD‐1 therapy. Such understanding will aid patient stratification and the rational design of combination therapies. It is also becoming clear, however, that Treg cells within tumours exhibit distinct biological features to both Tconv cells and Treg cells in other tissues. These distinct features provide the opportunity for development of targeted immunotherapies with greater efficacy and reduced potential for inducing systemic toxicity. [ABSTRACT FROM AUTHOR]

Describes a device for preparing cell spreads. Steps involved in preparing a suitable cell suspension; Features of the apparatus used in the process; Instrument's use of centrifugal force to speed up the sedimentation of the cells.

This study addresses itself to the problem of antibody formation in vitro by mouse splenic B lymphocytes enriched for reactivity to the hapten NIP by the hapten-gelatine binding and melting technique of Haas and Layton (1975). Small numbers of NIP-gelatine-bound B cells were placed in micro- cultures either by bulk dispensing of dilute cell suspensions, or by micromanipulation under direct microscopic visualization. Antibody formation was induced by the T cell-independent hapten-protein conjugate NIP-polymerized flagellin, using 104 thymus cells per microlitre as 'filler' cells. The frequency of precursors of NIP-specific antibody- forming cells among bound cells was about 2.2 × 10-2 (one cell in forty-five) by both statistical and direct evaluation, after adjustment for a background frequency of 6-10 × 10-8 precursors in the thymus filler cells. Single clones commenced antibody secretion asynchronously, as shown by the fact that the incidence of positive cultures continued to rise over the whole three days of culture, and that very small clones of one to four plaque-forming cells (PFC) were still found on day 3. The mean PFC number per positive culture rose from 1.2 at day 1 to 4.7 at day 2 and about 20 at day 3. Negative feedback, presumably mediated by antigen-antibody complexes, was shown to be a powerful effect in microcultures containing bound cells. It was evident with 250 cells per well (five clones) and the effect was progressive, such that with 10⊃ bound cells per well, plaque numbers were 40-50 per cent of their potential optimum; with 104, 10 per cent, and 105, 1 per cent. With routine techniques of harvesting of cultured cells, a failure to disperse PFC uniformly into single cells was noted. Groups of two or more large cells of very similar morphology were frequently observed at the centre of haemolytic plaques. Micromanipulation studies revealed that essentially all large cells at the centre of plaques were PFC. It was found that a routine plaque count underestimated the true PFC number per culture by a factor of 2. In the absence of negative feedback, the system is capable of generating one PFC per two input B lymphocytes. This is by far the most efficient plaque- generating system yet described, and contrasts with a yield of one PFC per 104 input cells in most typical tissue culture systems. Reasons for believing that both the culture and the enrichment systems can be further improved are discussed, and the potential of the method for understanding the cell and molecular biology of lymphocyte triggering is described. [ABSTRACT FROM AUTHOR]

The effects of human α2 macroglobulin (α2M) on locomotion of human neutrophils and monocytes in micropore filter assays in vitro were studied. Native α2M had no effect on cell locomotion. In contrast, α2M which had been modified by interaction with proteases (trypsin, collagenase), or with ammonium sulphate, stimulated locomotion of both cell types. The degree of locomotory response induced in the cells by α2M correlated closely with changes in molecular conformation of α2M as estimated by measurements of binding of the fluorescent probe, l-anilinonaphthalene-8-sulphonic acid (ANS). However neutrophil locomotion stimulated by modified α2M appeared to be solely chemokinetic, whereas monocytes showed both chemokinetic and chemotactic responses to modified α2M. The reason for this difference in response between the two cell types is unclear, but it is reflected in the lack of specific binding of α2M-protease complexes by neutrophils. Earlier workers had shown specific binding of such complexes by mononuclear phagocytes. [ABSTRACT FROM AUTHOR]

The ability of C57BL, C3H, and A strain marrow cells to proliferate on transplantation into irradiated isogenic, F1 hybrid, and backcross progeny mice has been investigated by the spleen-colony technique and by measuring the newly-formed DNA in the recipient spleen with [131I] 5-iododeoxyuridine. Transplants of C57BL cells grew poorly in (A × C57BL) F1 and in (C57BL × C3H) F1 and reciprocal hybrids, as compared with isogenic and allogeneic hosts, whereas C3H and A strain marrow grafts were successful in isogenic, F1 hybrid and backcross recipients. In segregating backcross progeny, i.e. in offspring from F1 hybrid females mated to C57BL males, the frequency of success or failure of the C57BL grafts suggested that the trait was controlled by a single pair of genetic determinants at an autosomal locus. The latter is apparently linked with, or part of, the H-2 region in the IXth linkage group. The experimental evidence suggested also that the failure of C57BL haemopoietic cell grafts in H-2 heterozygotes was not related to exhaustion of donor cells by excess of recipient isoantigen but rather to lack of expression in the heterozygotes of histocompatibility-related growth requirements yet undefined. These requirements are specific for haemopoietic cells, but not for skin grafts, and resulted most probably from the effect of genetic (inter-allelic) interaction involving H-2 or an H-2-linked locus. [ABSTRACT FROM AUTHOR]

A small scale modified method of the immune adherence on monolayer cells grown in Falcon plastic ‘Microtest’ plates is described. This method is especially useful in mouse systems as it simplifies the washing procedure which is an indispensable step for removal of the anticomplementary activity present in mouse serum. Histocompatibility antigens and the surface antigen induced by the Moloney virus could be detected with this method. [ABSTRACT FROM AUTHOR]

Reports that balancing cell death and proliferation plays a key role in the maintenance of homeostasis and the prevention of cancer in all multicellular organisms. Functions of pro-apoptotic and antiapoptotic members; Number of exons that consists the gene; Assessment on the functional importance of B-Myb in the regulation of the bcl-2 gene.