Mixed-lymphocyte reactions

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

Hurks, H. M. et al., Differential suppression of the human mixed epidermal cell lymphocyte reaction (MECLR) and mixed lymphocyte reaction (MLR) by cis-urocanic acid, Photochem Photobiol 65, 616-621,1997. 

Immunosuppressive effects have been obtained in vitro with mercuric chloride. A marked inhibition of the mixed lymphocyte reaction in mice as well as PFC (plaque forming cell) response to SRBC (sheep red blood cells) by mercuric chloride [166] has been reported. Chronic exposure to mercury of rabbits gave immunosuppression, measured as low antibody titres to viral agents [167], A suppression of antibody production in chickens exposed to mercuric chloride has also been reported [168]. Furthermore, an inhibition of mitogenic response to PHA in lymphocytes by mercuric chloride has been obtained [169],... 

An enhancement of the mixed lymphocyte reaction in mice by nickel and an enhancement of DNA synthesis induced by B cell mitogen lipopolysacharide has been found [166] furthermore, nickel was able to enhance the murine in vitro PFC response to SRBC [166, 388]. 

In addition to surface molecules, the presence and/or absence of cytokine production by DCs is influenced by Tregs in a way that tolerance rather than immunity is induced. For example, in mixed lymphocyte reactions with CD25—CD4+ T-cell DCs produce large amounts of the proinflammatory... 

Rheumatoid arthritis Vitamin B is a potential agent in management of RA. It mainly acts by correcting abnormalities in RACD8-t T cells in autologous mixed lymphocyte reaction (AMLR). 

II. NITRIC OXIDE PRODUCTION IN RAT SPLENOCYTE MIXED LYMPHOCYTE REACTION... 

The thiol group can also be found in heterocyclic compounds such as 2-mercaptobenzothiazole (9) and echinoclathrine C (10). Compound 9 was isolated from the symbiont bacterium Micrococcus sp., which was obtained from the sponge Tedania ignis [13]. The pyridine alkaloid echinoclathrine C (10) and its S-acetylated derivative, echinoclathrine B (11), were isolated from the Okinawan sponge Echinoclathria sp. [14]. The position of the hydroxyl and acylamino group on the phenyl ring in echinoclathrines (11 and 10) was recently corrected [15]. Compound 11 showed weak immunosuppressive activity in the mixed lymphocyte reaction assay with an IC50 of 9.7 pg/ml [14]. 

Mixed lymphocyte reaction, in which the lymphocytes of one individual are mixed with and proliferate in response to allogeneic lymphocytes of another individual. 

It is preferable but not essential to screen PBMCs from different donors to identify a donor whose cells replicate HIV efficiently and do not carry the A 32 C025 mutation. Alternatively, leukocyte enriched buffy coats may be purchased from blood transfusion centers. Mixing PBMCs from two donors results in a mixed lymphocyte reaction which can increase cellular activation and hence HIV replication. 

Cellular responses, as measured by a mixed-lymphocyte reaction, cytotoxic T lymphocyte response, and NK cell activity, were all undiminished, and if anything, there was a slight increase in CTL and NK responses. As would be expected by the histologic profile and the known increases in cytokine and chemokine production associated with the administration of PS ODNs in rodents, in this series of experiments there was no diminution in immune response. Administering a mouse-specific ICAM-1 inhibitor produced reductions in mixed lymphocyte reactions. This inhibition was expected as this is one of the desired pharmacologic effects of reducing ICAM-1 expression. 

Table 1 Selected thieno[2,3-d]pyrimidine-2,4( 1 H,3H)-dione derivatives and their corresponding physical data. When evaluated for their effectiveness as IL-2 inhibitors using the human mixed lymphocyte reaction assay, all experimental agents had IC50 values less than 1 x 10 6M...

The mixed lymphocyte reaction (MLR) test was performed in 96-well flat-bottomed microtiter plates. Selected experimental agents were prepared as 10 mM stock solution in DMSO and a 50-fold dilution of this was prepared in RPMI. Serial dilutions were prepared from this subsequent solution and 10 xl of the diluted stock was added to the well to give concentrations in the assay starting at 9.5 xm. In each well was placed 1.5 x 105 donor cells to give a final volume of 0.2 ml RPMI 1640 medium supplemented with 10% human serum, 2mM L-glutamine, and penicillin/streptomycin. Cells were incubated at 37°C in a humidified atmosphere containing 5% carbon dioxide for 120 hours. 3H-Thymidine (0.5 xCi) was added in the final 6 hours of incubation and cell radioactivity levels determined, which were indicative of T-cell proliferation. 

Panayi GS, Mills MM. Second-line drug treatment in rheumatoid arthritis associated with depressed autologous mixed lymphocyte reaction. Rheumatol Int 1986 6(l) 25-9. 

Romain, P.L. and Lipsky, P.E. (1983). Immunc obulin secretion during the autolc ous mixed lymphocyte reaction in man. J. Immunol. 130, 1146-51. 

A decrease in virus growth has been observed in mixed cultures, possibly resulting from mixed lymphocyte reactions. Thus, it is not advisable to not mix individual blood samples either before or after lymphocyte purification. 

The anti-inflammatory and immunosuppressive properties of berbamine and tetrandrine were compared. These comparative in vitro studies demonstrated that tetrandrine had significantly greater suppressive effects on adherence, locomotion and 3H-deoxyglucose uptake of neutrophils, as well as the mitogen-induced lymphocyte responses and mixed lymphocyte reactions. In addition, tetrandrine displayed anti-oxidant activity while berbamine did not. However, berbamine showed a significantly greater capacity for inhibition of NK cell cytotoxicity. These results indicated that tetrandrine was superior to berbamine in most aspects of anti-inflammatory and immunosuppressive activity [190]. 

Theodore AC, Center DM, NicoU J, et al. CD4 ligand IL-16 inhibits the mixed lymphocyte reaction. J Immuno 1996 157 1958-64. 

Lymphotoxicity (cytotoxicity or functional impairment, e.g., proliferation upon anti-CD3 or anti-CD28 stimulation) [7] Human peripheral blood lymphocytes (whole blood or PBMC) or rodent splenocytes are typically used. Polyclonal stimuli include anti-CD3, anti-CD28, plant lectins such as concanavalin A (ConA) and phytohemagglutinin (PHA), superantigens etc. Mixed lymphocyte reactions possible but less used for immunotoxicity... 

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