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J Punnonen

Publications and source records attributed to J Punnonen.

62 records · Page 4Linked to original sources
PubMed1989

Interleukin 2 and interferon-gamma affect human B cells at different stages of activation.

We studied the effects of recombinant interleukin 2 (rIL 2), interferon-alpha (rIFN-alpha) and interferon-gamma (rIFN-gamma) on proliferation and IgM synthesis of highly purified tonsillar B cells either without in vitro preactivation or after activation with Staphylococcus aureus Cowan 1 (SAC). Only rIL 2 affected tonsillar B cells not preactivated in vitro. It induced both proliferation and differentiation of B cells in a dose-dependent manner. rIL 2 induced proliferation of even Tac-negative B cells, but statistically significant responses were obtained only at high concentrations. The response was found also when no serum supplement was used in the culture medium. The finding suggests that tonsillar B cells express IL 2 receptors distinct from Tac antigen. When the cells were activated with SAC, significant proliferation was also found in response to rIFN-gamma. However, rIFN-gamma induced no IgM synthesis even after activation with SAC. rIFN-alpha affected neither B cell proliferation nor differentiation regardless of whether the cells were activated with SAC or not. Our results suggest that IL 2 can induce proliferation of activated B cells, but IFN-gamma only enhances proliferation of actively cycling B cells.

B-Lymphocytes↗
PubMed1989

The role of interleukin 2 in the regulation of proliferation and IgM synthesis of human newborn mononuclear cells.

The effect of interleukin 2 (IL-2) on cord blood mononuclear cells (CBMC) was studied, with special reference to B cell function. The study shows that CBMCs proliferate in response to recombinant interleukin 2 (rIL-2) without in-vitro preactivation. The response was also detected when whole blood cultures were used. CBMCs not preactivated in vitro proliferated in response to rIL-2 even after T cell and monocyte depletion. Thus, rIL-2 affects both non-T cells and T cells of newborns without preactivation in vitro. IL-2 receptors on unstimulated CBMCs appear to be distinct from Tac antigen, as the mean number of Tac antigen-positive cells among CBMCs was only 0.8%. Furthermore, rIL-2 inhibited PWM-induced proliferation and the response was more prominent in newborns than in adults. Thus, rIL-2 seems to cause a higher increase of suppressor cell function in CBMCs than in adult peripheral blood mononuclear cells. Neither rIL-2 nor Staphylococcus aureus Cowan 1 (SAC) stimulated any IgM synthesis, but a dose-dependent IgM synthesis was obtained by combining SAC and rIL-2. Alone, however, rIL-2 appears to be an insufficient factor to induce differentiation of SAC-activated cord blood B cells, as no IgM production in response to rIL-2 occurred in T cell and monocyte-depleted cell populations. The results of this study suggest both increased suppressor cell function and intrinsic B cell deficiency as causes of a weak humoral immune response in newborns.

B-Lymphocytes↗
PubMed1988

Recombinant interleukin 2 inhibits pokeweed mitogen-induced proliferation of human adult peripheral blood and cord blood mononuclear cells.

We studied the effects of recombinant interleukin 2 (rIL-2) on pokeweed mitogen (PWM)-induced proliferation of unfractionated human mononuclear cells from the peripheral blood (PBMCs) and cord blood (CBMCs). rIL-2 was found to inhibit PWM-induced proliferation of both PBMCs and CBMCs in a dose-dependent manner. The response was statistically significant at concentration 10 U/ml. The inhibition of adult PBMC proliferation was relatively mild, but in newborns up to 75% inhibition was found. The inhibitory effect of rIL-2 was best detectable at day 4, at the same time as PWM-induced proliferation peaked. However, also at days 8 and 10, the response induced by PWM plus rIL-2 was much lower than that induced by rIL-2 alone. These finding suggest that the inhibition was due to rIL-2-mediated stimulation of the function of PWM-activated suppressor cells. CD8+ T cells were, however, not alone responsible for the rIL-2-induced inhibition of PWM-induced proliferation, since the responses were essentially similar independent of whether CD8+ T cells were present or absent. In addition, the release of interferon-gamma (IFN-gamma) in response to rIL-2 was not a major cause of the inhibitory effects, because rIL-2 inhibited PWM-induced proliferation of CBMCs, which are deficient in producing IFN-gamma. Our results provide novel data to the ongoing discussion of IL-2 as a down-regulator of immune functions.

Adult↗
PubMed1988

The tonsils are superior to the peripheral blood as sources of mononuclear cells for B-cell purification.

Various methods for B-cell purification from mononuclear cells of the peripheral blood and tonsils were evaluated. L-leucine methyl ester was found to be the best method for monocyte depletion when B cells were isolated. Purification of B cells by negative selection methods from peripheral blood mononuclear cells (PBMCs) resulted in cell populations containing less than 40% B cells. This was partly due to significant increase in the relative number of large granular lymphocytes during the purification procedures. However, when T cells and monocytes were depleted from tonsillar mononuclear cells (TMCs), 84.6% of the remaining cells were B cells. The cell populations isolated from PBMCs and TMCs by negative selection methods differed from each other also in their responsiveness to pokeweed mitogen. Positive selection methods, such as panning and cell sorting by flow cytometer, resulted in good purities with both PBMCs and TMCs. However, the cell yields with the positive selection methods were always very low. It is concluded that the tonsils should be favoured as sources of B cells when negative selection methods are used. When peripheral blood B cells are wanted, positive selection methods should be favoured.

B-Lymphocytes↗
PubMed1987

Recombinant interleukin 2 induces proliferation and differentiation of human B lymphocytes.

Highly purified normal human tonsillar B lymphocytes were cultured with recombinant IL 2 (rIL 2). The responses were minimal when the cells were cultured with rIL 2 alone. Dose-dependent proliferation and differentiation into immunoglobulin-secreting cells were found when the cells were simultaneously activated with Staphylococcus aureus Cowan I (SAC). T cells were not found to proliferate in these cultures. B-cell responses were not augmented when 16% T cells were added to the B-cell population. In contrast, B-cell proliferation and Ig secretion were significantly enhanced by adding 0.5% T cells when cultured in the presence of pokeweed mitogen (PWM). Moreover, B-cell stimulation by rIL 2 was detected at very low cell densities. It is concluded that IL 2 directly affects the function of activated B cells.

B-Lymphocytes↗
PubMedDate not supplied

Inhibition of human IgE synthesis in vitro and in SCID-hu mice by an interleukin-4 receptor antagonist.

In the present study, it is shown that a human interleukin (IL)-4 mutant protein (IL-4.Y124D) acts as a potent IL-4 and IL-13 receptor antagonist. Human (h) IL-4.Y124D efficiently inhibits both IL-4- and IL-13-induced IgE production in vitro. In addition, hIL-4.Y124D strongly inhibits ongoing human IgE synthesis in SCID-hu mice. These inhibitory effects are specific, since human IgG levels were not significantly affected. These results confirm the notion that the IL-4 and IL-13 receptor share a common component, which is required for signal transduction. In addition, they show that relatively large antagonistic polypeptides, such as hIL-4.Y124D have potential clinical utility in reducing IgE-mediated allergic diseases.

Animals↗