ABSTRACT
We have compared the responses of purified neonatal and adult B lymphocytes to stimulation by anti-Ig antibodies, which are functional analogues of Ag, and by Th cells. Neonatal B cells are markedly deficient in proliferative responses to anti-Ig antibodies + IL-4 or to anti-Ig conjugated to dextran, both of which induce strong proliferation of adult B cells in the absence of T lymphocytes. Anti-Ig antibodies actually inhibit the functional responses of neonatal B cells, even to polyclonal stimuli such as LPS. However, Th cells induce both proliferation and Ig secretion by neonatal B cells in the presence of Ag that bind to B cell Ig and are subsequently presented by the B cells. Thus, in neonatal B lymphocytes, cross-linking of membrane Ig in the absence of Th cells has a net inhibitory effect, and this inhibition is overcome by T cell help. These results also suggest that unresponsiveness or tolerance to thymus-independent Ag is induced in the B cells themselves, but tolerance to thymus-dependent proteins resides primarily in the T cell compartment.
Subject(s)
Antibodies, Anti-Idiotypic/immunology , B-Lymphocytes/immunology , Immune Tolerance , T-Lymphocytes, Helper-Inducer/immunology , Aging/immunology , Animals , Animals, Newborn/immunology , B-Lymphocytes/metabolism , Calcium/analysis , Cell Division/drug effects , Dose-Response Relationship, Immunologic , Histocompatibility Antigens Class II/biosynthesis , Immunoglobulins/metabolism , In Vitro Techniques , Interleukin-4/immunology , Interleukin-4/pharmacology , Lipopolysaccharides/metabolism , Lymphocyte Activation/immunology , Lymphocyte Cooperation , Receptors, Interleukin-2/pharmacologyABSTRACT
On the basis of previous data that 1,25(OH)2D3 suppressed both helper and suppressor activities of CD4 and CD8 cells in the pokeweek mitogen-stimulated culture, we examined the further effect of 1,25(OH)2D3 on both cells to define how 1,25(OH)2D3 is involved in the deterioration of their functions. 1,25(OH)2D3 suppressed the pokeweed mitogen and phytohemagglutinin-induced DNA synthesis of CD4 and CD8 cells. The suppression by 1,25(OH)2D3 of DNA synthesis was caused by a time lag in reaching maximal response. 1,25(OH)2D3 also suppressed interleukin-2 production of CD4 and CD8 cells. 1,25(OH)2D3 did not, however, affect their interleukin-2 receptor expression detected within 24 hr after phytohemagglutinin stimulation. In addition, 1,25(OH)2D3 failed to suppress DNA synthesis of CD4 and CD8 cells when cultured with a large amount of interleukin-2. Suppression by 1,25(OH)2D3 of proliferation and interleukin-2 production in CD4 and CD8 cells would bring about the decrease of their helper or suppressor functions by inhibiting their expansion or maturation.
Subject(s)
Antibody-Producing Cells/drug effects , B-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/immunology , Calcitriol/pharmacology , T-Lymphocytes, Helper-Inducer/physiology , T-Lymphocytes, Regulatory/physiology , Antibody-Producing Cells/ultrastructure , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/ultrastructure , DNA/biosynthesis , DNA/drug effects , Humans , Interleukin-2/metabolism , Interleukin-2/physiology , Lymphocyte Activation/drug effects , Phytohemagglutinins/pharmacology , Pokeweed Mitogens/pharmacology , Receptors, Interleukin-2/pharmacology , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/ultrastructure , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/ultrastructureABSTRACT
Very recently, it has been reported that interleukin-1 (IL-1) has an inhibitory effect on progesterone production by porcine granulosa cells in vitro. In the present study we investigated the presence of IL-1 or IL-1-like activity in porcine ovarian follicular fluids (FF) as the first step in elucidating the physiological role of IL-1 in follicular growth and maturation. Since IL-1 and IL-1-like substances have interleukin-2 receptor (IL-2R)/p55(Tac)-inducing activity (TIA), we determined the TIA in the FF by means of a highly sensitive TIA assay using flow cytometry. TIA was significantly higher (P less than 0.01) in the FF of small follicles than in those of medium-sized and large follicles. A significant negative correlation (P less than 0.05) was apparent between TIA and 17 beta-estradiol concentration in the FF. The conditioned media of porcine granulosa cells also showed TIA. Of these conditioned media, those from small follicles exhibited higher TIA than those from medium-sized and large follicles. TIA in the conditioned media decreased rapidly as the culture period was extended. Sex steroids such as 17 beta-estradiol, progesterone, testosterone, and androstenedione had no effect on IL-2R/p55(Tac) induction. These results indicate that porcine granulosa cells produce the IL-2R/p55(Tac)-inducing factor, the activity of which decreases in association with the maturation of the follicles. Because of the heterogeneity of IL-2R-inducing factors, the relationship between TIA in the FF and IL-1 should be elucidated. We discuss the possibility that this factor may play a role in follicular maturation and that enhancement of IL-2R/p55(Tac) expression by this factor may contribute to the local defense mechanism in ovarian follicles.
