Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolerance of MHC class II alloantigens can be achieved by intravenous injection of semiallogeneic hematopoietic cells into neonatal mice. Lymphoid cells of tolerant mice fail to proliferate or secrete interleukins IL-2 or IL-4 when stimulated in vitro with tolerogen. Since the lymphoid organs of B10.T(6R) tolerant mice contain normal levels of I-E reactive (V beta 11+) CD4+ T cells, deletion of alloreactive T cells does not appear to be the mechanism involved in the tolerance induction. To test whether T cells from tolerant animals can become activated under conditions that do not involve alloantigen stimulation, we stimulated these cells with immobilized anti-V beta 11 antibodies. Spleen cells from grafted tolerant and rejector mice proliferated in response to anti-V beta 11+ antibodies, suggesting they were not inert. We then tested whether V beta 11+ T cells from grafted mice can be induced to proliferate following stimulation with alloantigen in vivo. We adoptively transferred T cells from grafted tolerant and rejector mice into irradiated (B10.AQR x B10.T(6R))F1 mice and harvested the lymphoid organs after 65 h. Cells from both grafted tolerant and rejector mice underwent blast transformation, but only cells from rejector mice proliferated when exposed to immobilized anti-V beta 11 antibodies. The failure of V beta 11+ cells from tolerant mice to proliferate after in vivo stimulation may be because they are apoptotic. To test this hypothesis, spleen cells from naive or neonatally tolerized (with (B10.AQR x B10.T(6R))F1 cells) B10.T(6R) mice were adoptively transferred into irradiated (B10.AQR x B10.T(6R))F1 mice and bcl-2 expression was analysed in harvested V beta 11+ cells. Large cells recovered from recipients of naive 6R cells expressed bcl-2 mRNA. By contrast, large cells harvested from recipients of tolerized 6R cells did not express bcl-2 mRNA, suggesting bcl-2 mRNA expression was downregulated in these mice. Moreover, in another experiment, large V beta 11+ cells from grafted tolerant animals recovered after transfer into irradiated (B10.AQR x B10.T(6R))F1 mice did not express the bcl-2 protein as determined by flow cytometry, and contained fragmented DNA as assessed by the TUNEL method. Taken together, these data suggest that MHC class II tolerant T cells undergo apoptosis upon re-exposure to tolerogen in vivo.
 ...
PMID:MHC class II tolerant T cells undergo apoptosis upon re-exposure to tolerogen in vivo. 876 18

Chlorophyllin (CHL) was earlier shown to reduce the level of intracellular ROS and apoptosis induced by ionizing radiation and 2,2'-azobis(2-propionimidinedihydrochloride) (AAPH). In the present studies, the effect of CHL on radiation-induced immunosuppression and modulation of immune responses in mice was examined. Chlorophyllin inhibited the in vitro lymphocyte proliferation induced by concanavalin A (Con A) in a dose dependent manner at doses>or=50 microM. At lower doses (10 microM) CHL significantly inhibited activation induced cell death (AICD) in Con A stimulated spleen cells. Spleen cells obtained from CHL treated mice showed an inhibition of response to Con A depending on dose of CHL and the time after its administration. Spleen cells obtained from CHL treated mice (24 h) showed lower inhibition of response to Con A following in vitro (5 Gy) as well as whole body irradiation (2 Gy). The expression of antiapoptotic genes bcl-2 and bcl-xL was up-regulated in these cells. Chlorophyllin treatment of mice led to splenomegaly and increase in the number of peritoneal exudate cells (PEC). The numbers of T cells, B cells and macrophages in the spleen were also increased. Increased phagocytic activity was seen in PEC obtained from CHL treated mice. Most importantly, CHL administration to mice immunized with sheep red blood cells (SRBC) augmented both humoral and cell-mediated immune responses.
 ...
PMID:Antiapoptotic and immunomodulatory effects of chlorophyllin. 1661 80