Thymic humoral factor gamma 2 (THF-gamma 2), an octapeptide essential for immune regulation, was purified from calf thymus. The purification of THF-gamma 2, monitored in vitro and in vivo in mouse splenocyte proliferation assays, was achieved by gel filtration of low molecular weight thymus extracts followed by ion-exchange chromatography and sequential reversed-phase high-performance liquid chromatography. The process yielded 5 micrograms of THF-gamma 2/1000 kg of thymus tissue. The concentration of THF-gamma 2 required for augmentation of lymphocyte proliferation and interleukin 2 production was 5 ng/mL in vitro and 10 ng/kg per mouse in vivo. THF-gamma 2 has the amino acid sequence Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu. The proposed structure has been confirmed because a peptide was synthesized on the basis of this sequence that showed activity identical with that of the biological molecule. It shows no homology to the amino acid sequence of other thymic hormones nor is it part of any peptide or protein of known sequence. THF-gamma 2 retains essentially all of the biological activity of the thymus extract from which it is derived.
The phenotypic distribution and immune reactivity of T lymphocyte sub-populations from peripheral blood of 50 patients with urological cancer were determined. Included were 36 patients with bladder transitional cell carcinoma, 7 patients with renal cell carcinoma and 7 patients with prostatic carcinoma. Thirty-eight age-matched patients with benign urological disease served as controls. A depression in immune competence was found in the group of male patients with infiltrating bladder cancer. In more than 50% of the patients with infiltrating bladder carcinoma, the T helper (CD4) subset was reduced with a concomitant inversion in the CD4/CD8 ratio and impairment in the T cell function as determined by the ability to proliferate upon phyto-hemagglutinin and concanavalin stimulation. Patients with superficial bladder carcinoma, as well as those with renal cell carcinoma had an immune profile similar to that of the control group. The group of patients with prostatic carcinoma had higher mean CD4/CD8 ratios than the control group, resulting from decreased suppressor/cytotoxic cells. Our results have indicated that the characterization of T cell subset and lymphocyte activity correlated well with the histopathologic stage of patients with bladder carcinoma. Thus, the determination of the CD4/CD8 ratio may prove a valuable method for monitoring patients with bladder carcinoma, in addition to serial urine cytology, random urothelial biopsies and flow cytometry.
CBA/J female mice mated with DBA/2J males show a high incidence of fetal resorptions. This paper presents data demonstrating that nonspecific immunopotentiation by complete Freund adjuvant (CFA) reversed pregnancy loss in CBA/J mothers. Immunization of more than 70 CBA/J females mated with DBA/2J males with CFA reduced the incidence of fetal resorption from 27.3 +/- 1.9 to 7.9 +/- 1.5%. The injection of Thymus Humoral Factor known to be a potent T cell stimulator did not reduce the number of fetal resorptions. The route of CFA distribution was found to be important--only foot pad injections were effective in fetal protection, whereas i.p. treatment did not reduce fetal resorptions. Fetal protection could be transferred by splenocytes of CFA-injected CBA/J mothers (9.6 +/- 5.0% fetal resorptions). Sera from treated CBA/J mice could not cause such an effect (17.6 +/- 4.6 vs. 21.3 +/- 6.1 in control animals). Thus, stimulation of the maternal immune system by nonspecific immunopotentiators can improve reproductive performance of this mouse combination which has an increased rate of pregnancy loss. Possible mechanisms of this fetal protection are discussed.
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