Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.

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Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Regulation of the immune response by prostaglandins.

The discovery that the thymus was involved in the development of the immune system (Miller, 1961; Archer et al, 1962; Jankovic et al, 1962) ushered in the “golden age of ‘thymology’” (Miller, 1967). A second golden age (Miller, 1967) began with the discovery that thymus-derived lymphocytes [soon to be christened T cells (Roitt et al, 1969)] did not themselves make circulating antibodies, but rather assisted other nonthymus-derived lymphocytes to do so (Miller and Mitchell, 1969; Davies, 1969; Claman and Chaperon, 1969). This second class of lymphocytes was christened B cells (Roitt et al, 1969), a term with sufficient ambiguity to gain the acceptance of those who thought these cells differentiated to a functional state in mammalian bone marrow and those who thought a mammalian equivalent of the bursa of Fabricius played a role in their differentiation.

T cell control of antibody production.

After mice were exposed to a daily auditory stressor for varying lengths of time, the responses of their splenic lymphoid cells in vitro were assessed. Both the blastogenic activity of concanavalin A or lipopolysaccharide and the ability of immune lymphocytes to lyse P815 target cells showed the same patterns of immunosuppression and enhancement.

https://science.sciencemag.org/content/sci/196/4287/307.full.pdf

Stress-induced modulation of the immune response

Stress and cancer.

The present study confirms and extends the finding that DA rat spleen cells include a subpopulation of adherent cells which act at high doses of phytohemagglutinin (PHA) or concanavalin H (ConA) to suppress DNA synthesis by other cells. Suppressor activity is lacking in spleens of doubly thymus-deprived rats. Mitomycin C treatment does not reduce the suppressor activity of normal whole spleen. It is inferred that the suppressor cell is a T lymphocyte or depends for its action on the presence of T lymphocytes and that its action does not require cell proliferation. DNA synthesis is much more affected by suppression at high mitogen levels than RNA or protein synthesis. A parallel is drawn between the separate regulation of DNA synthesis and other macromolecular synthesis in lymphocytes and so-called “pleiotypic” effects in other types of cells. Spleen cells of young rats give a relatively low response ( 3 H-thymidine uptake) to optimal or supraoptimal doses of PHA, which is markedly increased by removal of adherent cells on glass wool and is not affected by addition of purified macrophages. In contrast spleen cells of older animals give a high response, which falls when adherent cells are removed but is restored to the original level by addition of macrophages. It is concluded that older animals9 spleens differ from those of younger rats by a variable loss of suppressor cells and an increasing macrophage dependence of PHA-responsive cells. The former may account for the reported increase in autoantibody formation with age. Reactivity of cells of a given age was not affected by culturing them in young or old rat serum pools, respectively. Stress or injection of hydrocortisone acetate result in loss of suppressor cell adhesiveness to glass wool and increased macrophage dependence of PHA-responsive cells at 5 days. At 2 to 3 weeks there is a return to normal levels of adhesiveness and macrophage dependence, accompanied by a marked increase of suppressor activity. The 5-day changes are thought to reflect direct effects of steroid on the properties of T lymphocyte membranes, and the later changes altered levels of thymus hormone or possibly a surge of “post-thymic cells” into the peripheral lymphoid organs.

The splenic suppressor cell. I. Activity of thymus-dependent adherent cells: changes with age and stress.

Regulation of lymphocyte responses in vitro. V. Suppressor activity of adherent and nonadherent rat lymphoid cells.

In vitro responses of rat lymphocytes following adult thymectomy. II. Increased inhibition by splenic adherent cells of responses to phytohemagglutinin.

Inbred DA rats thymectomized at 8 weeks of age showed a marked decrease in in vitro reactivity of spleen cells to phytohemagglutinin-P (PHA) and concanavalin-A, appearing as early as 3 days and vanishing by 35 to 40 days. This change could not be explained by enlargement of the spleen. However, there was a proliferation of blasts in the splenic marginal zones at 1 to 2 weeks, but not at other times. Peripheral (popliteal, inguinal, and axillary) and mesenteric lymph nodes showed a similar effect. This effect was of lesser magnitude and appeared only 20 days after thymectomy, with recovery at the same time as the spleen, and was not observed in rats thymectomized at 4 weeks of age. Spleen cells after thymectomy showed a relatively inconstant decrease in reactivity to hemiallogeneic cells, while the decrease with both types of lymph node cells was, if anything, greater than the decrease in PHA reactivity. The evidence suggested that these findings could not be simply attributed to loss of a putative thymus-derived lymphocyte subpopulation.

Hugo Folch

Papers

The splenic suppressor cell. I. Activity of thymus-dependent adherent cells: changes with age and stress.

Regulation of lymphocyte responses in vitro. V. Suppressor activity of adherent and nonadherent rat lymphoid cells.

In vitro responses of rat lymphocytes following adult thymectomy. II. Increased inhibition by splenic adherent cells of responses to phytohemagglutinin.

In Vitro Responses of Rat Lymphocytes Following Adult Thymectomy: I. Rapid Decrease and Recovery of Responses to Mitogens and Hemiallogeneic Cells