Immune down-regulation

IFN-y also directly modulates the immune response by affecting growth, differentiation and function of both T- and B-lymphocytes. These effects are quite complex and are often influenced by additional cytokines. IFN-y acts as a growth factor in an autocrine manner for some T cell sub-populations, and it is capable of suppressing growth of other T cell types. It appears to have an inhibitory effect on development of immature B-lymphocyte populations, but it may support mature B cell survival. It can both up-regulate and down-regulate antibody production under various circumstances. 

NE and EPI stimulate a- and (TAR on the cell surface of target tissues. P2-AR are expressed on almost all types of immune cells, with the notable exception of T-helper (Th)2 clones [3], P-AR on immunocytes are coupled with Gs proteins and adenylate cyclase, with subsequent activation increasing intracellular adenosine 3 , 5 -cyclic monophosphate (cAMP) and protein kinase A (PKA). Under normal conditions, P-AR cell surface expression up- and down-regulates in response to reduced and increased catecholamine... 

Consistent with this hypothesis are data from a study with mice. Social disruption of groups of 5 male BALB/c mice was shown to increase aggression among cohorts, activate the HPA axis, and reactivate latent HS V-1 in more than 40% of latently infected mice.46 In contrast, restraint stress, which can down-regulate the innate and HSV-1 specific immune response, did not reactivate latent HSV-1.47 HPA activation, as measured by serum corticosterone levels, was comparable using both types of stressors. 

One likely reason for the prevalence of helminths is their undoubted ability to down-regulate the host immune system at both the antigen-specific and polyclonal levels [3], In many chronic diseases, such as schistosomiasis and lymphatic filariasis, peripheral blood T cells show dramatically impaired parasite antigen-specific responsiveness [4], as discussed in more detail below. Moreover, from early reports of immunosuppression in animal models of infection, to studies in Africa linking vaccine failure to heavy helminth infection, there is clear evidence that infections can diminish reactivity to bystander antigens, particularly with increasing intensity of... 

Wynn, T.A., Cheever, A.W., Williams, M.E., Hieny, S., Caspar, P., Kuhn, R., Muller, W. and Sher, A. (1998) IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is not required for immune down-modulation of chronic disease. The Journal of Immunology 1 60, 4473 1480. 

Grawunder, U., Leu, T.M.J., Schatz, D.G., Werner, A., Rolink, A.G., Melchers, E, Winkler, T.H. (1995). Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement. Immunity 3,601-608. 

TGF-/31 was also evaluated with NOD mice for the prevention of autoimmune diabetes, since it down-regulates many immune responses (Piccirillo et al., 1998). In TGF-/31 expression plasmid, pCMV-TGF-/ 1, the mTGF-/31 cDNA is under the transcriptional control of a CMV promoter/enhancer. Intramuscular injection of the plasmid showed TGF-/51 mRNA expression in skeletal muscle cells, as well as an increased level of TGF-/31 in the plasma of treated mice. Administration of pCMV-TGF-gl / was effective in protecting NOD mice from insulitis and diabetes. In addition, there was a decreased expression of IL-12 and IFN7 mRNA in the pancreas of protected mice. 

Although this treatment has been available for idiopathic thrombocytopenic purpura for several years, its mechanism of action is not understood. Removal of IgG and IgG-containing immune complexes does not explain its effects in rheumatoid arthritis. The most recent hypothesis for this treatment s mechanism of action is down-regulation of B cell function through the release of small amounts of staphylococcal protein A complexed with immunoglobulins. 

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