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Background: Clinical trials on multiple sclerosis with repeated injections of monoclonal antibodies depleting CD4 + T cells have not resulted in much success as a disease therapy. Here, we developed an immunotherapy for EAE in mice by combining a transient depletion of T cells together with the administration of neuron derived peptides., Methods: EAE was induced in SJL and C57BL/6 mice, by proteolipid protein peptide PLP 139-151 (pPLP) and myelin-oligodendrocyte glycoprotein MOG 35-55 (pMOG) peptides, respectively. Anti-CD4 and anti-CD8 antibody were injected intraperitoneally before or after peptide immunization. EAE scores were evaluated and histology data from brain and spinal cord were analyzed. Splenocytes were isolated and CD4 + , CD4 + CD25 - and CD4 + CD25 + T cells were purified and cultured in the presence of either specific peptides or anti-CD3 antibody and proliferation of T cells as well as cytokines in supernatant were assessed., Findings: This experimental treatment exhibited therapeutic effects on mice with established EAE in pPLP-susceptible SJL mice and pMOG-susceptible C57BL/6 mice. Mechanistically, we revealed that antibody-induced apoptotic T cells triggered macrophages to produce TGFβ, and together with administered auto-antigenic peptides, generated antigen-specific Foxp3 + regulatory T cells (T reg cells) in vivo., Interpretation: We successfully developed a specific immunotherapy to EAE by generating autoantigen-specific T reg cells. These findings have overcome the drawbacks of long and repeated depletion of CD4 + T cells, but also obtained long-term immune tolerance, which should have clinical implications for the development of a new effective therapy for multiple sclerosis. FUND: This research was supported by the Intramural Research Program of the NIH, NIDCR., (Copyright © 2019. Published by Elsevier B.V.)

The use of monoclonal antibody targeted therapy has changed the management of several diseases, including in hematology and immunology. The panel of the present available biotherapies allows a specific action at various stages of the immune response. Indeed, some of these molecules can target the naive T cell at the immunological synapse or the way of TH1, TH17 and regulatory T cell. Others may be more specific for the B cell and immunoglobulin. Some will even be active on both B and T cells.

Glucocorticoids exhibit anti-inflammatory, anti-allergic and immunosuppressive properties, which contribute to their beneficial therapeutic effects. The biological effects of their interaction with their soluble receptor have been investigated as well as their inhibitory effects on several proteins implicated in the inflammatory process and on the tissular steps of inflammation. In addition, glucocorticoids exert multiple inhibitory effects both on immunocompetent cells (mainly T-lymphocytes) and on cytokines. Their role on Th17 lymphocytes and regulatory T cells has been recently studied and could represent new mechanisms of action of these drugs., (Copyright © 2012. Published by Elsevier Masson SAS.)

Studies on probiotics had found a benefit in their use. That was attributed to a barrier effect at the intestinal mucosa. We tried a new immunephysiological explanation supported by murine works and in humans. Immune modulation by probiotic bacteria and induce IL10 producing regulatory T cells. Receptors DCSIGN and Toll dendrites cells interfere in the copresentation of antigens and generate an immune response modulation by regulatory T cells and their inhibitory cytokines TGFβ, IL10., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Polyclonal anti-lymphoyctes antibodies were first successfully used in the 1970 in organ transplantation, but ten years later, monoclonal antibodies (mAb) emerged as a new class of immunosuppressive agents in transplantation with the potential to target highly specifically immune cells responsible for acute rejection. Some have proved their efficacy, such as mAb recognizing CD3- and CD25-positive T cells and have been extensively studied in clinical trials. Others such as mAb against CD52 and CD20, are still under investigation; finally, the next challenge is, based on our improved understanding of the mechanisms of immune recognition and allograft rejection, to use these mAb either alone or in combination with standard immunosuppressive regimens to manipulate the allogenic response to reach antigen-specific tolerance desired in solid-organ transplantation.

We have studied the in vitro antibody response to a hapten of peripheral blood lymphocytes from 26 patients with rheumatoid arthritis and 7 ankylosing spondylitis. These patients had never received immunosuppressor drugs before or corticosteroids during the month before the test. They had failed to receive aspirin or non-steroid anti-inflammatory drugs for 72 hours before blood sampling. The control groups included respectively 38 healthy subjects and 24 patients hospitalized for non inflammatory disease. The antibody response of ankylosing spondylitis patients is comparable to that of controls ; on the opposite the response of patients with rhumatoid arthritis is significantly depressed in comparison with the three other groups. The weak response of lymphocytes in arthritis is not due to increased cell death in culture or to modified kinetics of the antibody response or to the appearance of a IgG secondary type response or a in vivo pre-activation. The lymphocytes of arthritis patients do not inhibit the response of normal lymphocytes when they are co-cultured. The observed response is identical to that obtained when control patient lymphocytes are co-cultured with normal lymphocytes. The function of suppressor T cells induced by Con A seems normal in spondylitis and arthritis.

The in vitro effect of various cephalosporins on T lymphocyte functions was studied. These antibiotics directly stimulated lymphokine production and significantly suppressed mitogen-stimulated lymphocyte transformation responses. Penicillin had no effect. Suppression of blastogenesis could be mediated through suppressor cell enhancement as indicated by: i) the significant suppressed lymphocyte transformation observed while using the dialyzed supernatant of cephalosporin-stimulated and cultured lymphocytes, ii) the enhanced blastogenesis, commonly ascribed to suppressor cell depletion, blunted by pre-incubation with cephalosporins, iii) the suppressed blastogenesis of allogenic responder cells in MLR by cephalosporin pre-incubated, mitomycin treated cells. An indirect effect through PgE2 release by macrophages cannot ruled out. The enhancement of suppressor activity by most of the cephalosporins might explain the smaller incidence of late hypersensitivity reactions observed with these antibiotics compared with penicillins.

A random study has been made on perennial atopic rhinitis patients divided into two homogeneous groups and treated with HH2 antagonists of different chemical structure: Cimetidine and Ranitidine. An identity of clinical and humoral results was noted in the two groups. This leads us to believe that the effects induced by the two drugs are linked to the properties of H2 antagonists and not to other potential action as hypothesised for Cimetidine by Drazen. The improvement in all subjective and objective parameters, decrease in total serum IgE, the delayed onset of clinical improvement and its duration in time, suggest that the vascular type action mechanism hypothesised by some Authors is quite secondary to the immunomodulatory one. H2 antagonists in fact induce, together with the clinical improvement and the total serum IgE decrease, a modulatory effect on the T-lymphocyte subsets with a variation in the OKT4/OKT8 ratio towards the latter subset that identifies the suppressor cells. Since lymphocyte histamine receptors are uniquely present on suppressor T-cell, it is on these the H2 antagonists would act, modulating the suppressive function positively.

Male DBA/2 Mice were kept on a magnesium deficient diet or a control diet. The antibody response of spleen cells, after in vitro immunization with Sheep red blood cells (SRBC) was determined comparatively in the two groups of Mice, from the 19th to the 22nd day of the diet. The effect of sodium periodate treatment on the induction of in vitro antibody suppressor cells was also studies. This treatment activated suppressor cells towards anti-SRBC response in the control group, but not in the Mg-deficient group (P less than 0.002). A greater sensitivity of periodate induced T suppressor cells to Mg deficiency is suggested by the present results.

Twenty patients with classical or proved rheumatoid arthritis were treated with Isoprinosine. 13 patients received a dose of 25 mg/kg/day and 7 received a dose of 50 mg/kg/day, continuously for 2 months and then discontinuously, 5 days every fortnight. The series being treated with 25 mg/kg/day (7 patients) have received treatment for 12 months. No side effects have been observed; the only reason for ceasing treatment was its ineffectiveness (after at least 3 months of administration). The dosage of the associated anti-inflammatory drugs did not need to be increased, but neither was it decreased. The authors conclude that Isoprinosine is largely ineffective clinically, on laboratory tests and in terms of immunology, at least with the therapeutic protocols tested here.