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Reaginic antibody formation in the mouse. VII. Depression of the ongoing IgE antibody formation by suppressor T cells.

The ongoing IgE antibody formation against ovalbumin (OA) in high responder mice was depressed by i.v. injections of either native or urea-denatured ovalbumin (UD-OA). Adoptive transfer experiments to determine the helper function of spleen cells from the treated animals showed that helper function for both IgE and IgG antibody responses diminished after treatment. Evidence was obtained that treatment suppressed the expansion of IgE-G memory cells. When the same treatment with OA or UD-OA was given to OA-primed mice before the appearance of IgE antibody in their serum, OA-specific splenic suppressor T cells were demonstrable. Thus, the transfer of splenic T cells from treated mice into normal mice suppressed the primary IgE and IgG antibody responses of the recipeints to DNP-OA. It was also found that the transfer of the splenic T cells from UD-OA-treated mice into OA-primed mice depressed ongoing IgE antibody formation in the recipients. The results suggested strongly that the decrease of helper function and the depression of ongoing IgE antibody formation by repeated injections of UD-OA was caused by generation of antigen (OA)-specific suppressor T cells.

Animals↗

Factor VIII concentrate inhibits T helper type 2 cytokine production in vitro: relevance to inhibitor antibody formation.

Inhibitor antibody formation in patients with haemophilia receiving factor VIII (FVIII) concentrate is a serious problem. T helper type 2 (Th2) cytokines are necessary for antibody production by B cells and have been shown to be produced predominantly by CD30(+)/CD45RO(+)/CD3(+) cells. We have previously shown that the Th2 cytokine, interleukin (IL)-6, is inhibited but IL-10 is upregulated, in the presence of plasma-derived FVIII (pdFVIII). To clarify further the overall effect of FVIII on Th2 cytokine production, the percentage of T cells expressing the CD30(+)/CD45RO(+)/CD3(+) Th2 phenotype was studied over 72 h and the production of the Th2 cytokines, IL-4 and IL-5, determined at 24 h in the presence of FVIII following whole-blood stimulation using multiparameter flow cytometry. The production of IL-4 and IL-5 by T cells was significantly inhibited in the presence of pdFVIII. The percentage of CD30(+)/CD45RO(+)/CD3(+) increased with stimulation of whole blood cultures over 72 h but was significantly inhibited by the presence of pdFVIII or TGF-beta at 72 h. The combined inhibitory effect of prednisolone (a commonly used immunosuppressive agent used to treat patients with inhibitors) with pdFVIII on T-cell CD30(+)/CD45RO(+) upregulation, was additive. There was no significant alteration in Th2 cytokine production or phenotype noted in the presence of recombinant FVIII (rFVIII) concentrate. Neutralizing antibody to TGF-beta significantly abrogated the inhibitory effects of pdFVIII on Th2 upregulation, indicating TGF-beta to be a major inhibitory component of pdFVIII on Th2 cytokine production. We now provide evidence that pdFVIII, by inhibiting Th2 cytokine production, may result in decreased antibody formation and may be more appropriate than rFVIII at reducing inhibitor formation. A clinical study needs to be undertaken to determine the significance of these in vitro findings.

Cell Culture Techniques↗

THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY. I. 19S AND 7S ANTIBODY FORMATION: DIFFERENCES IN KINETICS AND ANTIGEN DOSE REQUIREMENT FOR INDUCTION.

Rapid formation of poliovirus-neutralizing antibody was observed in the rabbit. 19S type antibody was detectable 8 to 12 hours following a single intravenous virus injection and the induction period was of the order of 4 to 5 hours or less. The production of 7S antibody had a longer lag phase (1(1/2) to 2 days) and it was formed at slower rate. The observed rate of early 19S and 7S antibody formation as well as the peak titers of the two antibodies were antigen dose dependent. Normal rabbit sera showed low neutralizing activity to several viral antigens in a sensitive assay system. Following intravenous inoculation of poliovirus either transitory ( 1 month) or enduring ((3/4) to 1(1/2) year) antibody formation resulted depending upon the dose of antigen employed. In transitory responses, which could be induced by a single small antigen dose, only 19S antibody was demonstrable and there was an abrupt cessation of antibody synthesis on day 4 or 5. In enduring responses, both 19S and 7S antibody were formed and the minimum antigen dose required for initiation of such a response was equal to the dose needed for induction of 7S antibody formation. Thus, enduring antibody formation was an all-or-none phenomenon depending upon whether or not 7S antibody formation was induced. The antigen dose requirement for induction of 7S antibody was much higher (by 50-fold or more) than that for 19S antibody. This allowed a determination of antigen dose regions, within which predictably transitory (19S) or enduring (19S + 7S) antibody formation was obtained. These pronounced differences in antigen dose requirement for induction and kinetics of formation of 19S and 7S antibody suggest that the same cells do not participate in the formation of the two antibodies.

Antibodies↗