CD4 Spleen Cells Research Articles

Altered T-Cell Phenotypes in Chronic Obstructive Pulmonary Disease

metalloproteases (MMPs) MMP-9 and MMP-2 in the lungs of immunized animals when compared with control rat lungs. Anti– endothelial cell antibodies recognize several endothelial cell epitopes, including vascular endothelial growth factor receptor (VEGFR)-2 and angiotensin-converting enzyme (ACE). Mice injected with anti–endothelial cell serum also develop emphysema. Lung morphometry of mice injected with anti–endothelial cell antibody showed 20% enlargement of alveolar airspaces over a 5-wk period as compared with normal rat serum–injected controls. Immunization also causes accumulation of CD4 T cells in the lung. Adoptive transfer of a pathogenic, spleenderived CD4 cell population into naive immune-competent animals also results in emphysema. Moreover, adoptive transfer of CD4 spleen cells into secondary syngeneic rats resulted in emphysema, even though these secondary rats had not been immunized with human umbilical vein endothelial cells (HUVEC). In this study, we show for the first time that humoral and CD4 cell–dependent mechanisms are sufficient to trigger the development of emphysema. Our data demonstrate that pathogenic CD4 T lymphocytes are necessary and sufficient in breaking a regulatory tolerance and causing emphysema in naive immunecompetent rats, suggesting the involvement of autoimmune mechanisms in alveolar septal cell destruction.

Adoptive transfer of CD4 spleen cells isolated from mice immunized with a 125 amino-acid fragment of H. pylori urease B reduces Heucobacter infection in recipient BALB/c mice

Mucosal immunization with a 125 amino-acid fragment of H. pylori urease B (HpUreB220_345) and cholera toxin (CT) is sufficient to prevent Helicobacter infection in BALB/c mice. Aim: To determine whether adoptive transfer of CD4 spleen cells isolated from mice immunized with HpUreB220_345 can confer protection to recipient BALB/c mice against Helicobacter infection. Methods: Donor BALB/c mice were nasally immunized with HpUreB220_345 and CT and infected with H. felis (Hf). CD4 spleen cells were transferred intravenously to recipient BALB/c mice (2xl 06/mouse), either directly or after in vitro stimulation with HpUreB 220_ 345. Recipient and naive mice (lO/group) were infected with Hf one day after transfer and sacrificed 2 weeks later. Infection status was determined by Urease Test (UT). p values were determined by WilcoxonlKruskalWallis test compared to control mice Results: Donor mice were split into protected (9/15) and unprotected animals (6/15) according to their UT (mean O~O and 0.5~0.1, respectively). Injection of CD4 from unprotected donors before Hf infection significantly reduced bacterial colonization compared to control infected mice. Adoptive transfer of CD4 from protected mice had no effect on the level of Hf infection. The difference in the efficacy of CD4 from protected and unprotected donors was significant (p=O.03). After in vitro stimulation with HpUreB220_345' CD4 spleen cells from both unprotected and protected donors decrease the level of bacterial infection in recipient mice Conclusions: Adoptive transfer of CD4 spleen cells from mice immunized with a 125 amino-acid fragment of urease B can decrease the level of Helicobacter infection in recipient mice. The fact that the CD4 cells from protected donor spleens need to be stimulated to exert an effect in recipients suggest that they are in lower number compared to unprotected donors, probably because most of them have already migrated to the stomach

Antagonistic interactions among T cell subsets of old mice revealed by limiting dilution analysis.

When CD4 spleen cells from old (but not young) mice are tested for Con A-induced proliferation in limiting dilution assays, the dose response curve shows a nonlinear relationship. We interpret these observations using a two-cell model, in which proliferation of one cell type (LPC1) can be blocked by a second cell type (LPC2), which can itself generate detectable proliferation only at high multiplicities. The two-cell model accounts for several observations: 1) the variation in curve shape as a function of incubation time; 2) the skewed distribution of wells scored as "negative" in cultures of old splenocytes; and 3) the initially antagonistic effects of old splenocytes titrated into cultures containing fixed numbers of young responders. To provide a further test of the two-cell model, ionomycin-resistant (CaR) and ionomycin-sensitive (CaS) cells were separated using a Percoll/ionomycin gradient. The CaR preparation, shown previously to consist largely of memory T cells, showed the dose curve predicted for the LPC2 cell type, whereas the CaS (naive) cells showed the single-hit kinetics postulated for LPC1 cells. Furthermore, mixtures of CaR and CaS cells from young mice reproduced the zigzag dose curve characteristically produced by unseparated cells from old mice. These data suggest that the spleens of both young and old mice contain two kinds of Con A-responsive CD4 cell: one that proliferates vigorously, and a second, calcium ionophore-resistant type that proliferates less well, that can interfere with proliferation of the first cell type, and whose frequency increases with age.