Immune-response gene control of cytotoxic T-cell responses to H-Y.
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Biomedical subjects
Publications and source records attributed to R D Gordon.
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C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.
1. Nine men aged 20-33 years with essential hypertension measured their own blood pressure at home, lying and standing, three times daily, under conditions of everyday living. The last 14 days' readings (eighty-four observations) from control and treatment periods of at least 4 weeks' duration were used to calculate mean pressures. 2. In eight patients, propranolol (40 mg thrice daily with meals) significantly lowered "mean blood pressure" (diastolic+1/3[systolic-diastolic]) but methyclothiazide (5 mg with breakfast) did not. In five subjects, prindolol (5 mg thrice daily with meals) significantly lowered "mean blood pressure" but methyclothiazide (5 mg with breakfast) did not. 3. In six subjects there was no significant difference between "mean blood pressure" when taking propranolol doses 120 mg with breakfast, 60 mg with breakfast and with the evening meal, and 40 mg with each meal. In five subjects there was no significant difference between "mean blood pressure" when taking metoprolol 200 mg with breakfast and 100 mg with breakfast and with the evening meal. In four subjects there was no significant difference between "mean blood pressure" when taking prindolol 30 mg with breakfast, 15 mg with breakfast and with the evening meal, and 10 mg with each meal. 4. In young males with essential hypertension, beta-adrenoreceptor blockers were more effective than a thiazide diuretic in lowering blood pressure, and were effective in a single daily dose.
Plasma testosterone, luteinizing hormone (L.H.) and follicle stimulating (F.S.H.) were measured before operation in 39 males, aged 26 to 53 years with 2 to 5 children, seeking vasectomy for contraceptive purposes. These measurements were repeated at 3 and 12 months after vasectomy. Levels of L.H. at 12 months were significantly higher than pre-vasectomy levels, suggesting some degree of decreased Leydig cell function. However, testosterone and F.S.H. levels were similar at the three sampling times. Continuing yearly measurements for at least 5 years are planned.
In young males with essential hypertension, propranolol and pindolol in small doses caused significant expansion of plasma volume (PV) after one month which did not prevent a reduction in BP. With higher doses, changes in PV were inconsistent and reductions in plasma renin activity (PRA) and 24-hour aldosterone excretion (AE) not closely related to BP changes. The effects of beta-adrenoreceptor blocking drugs on PV, PRA, and AE do not appear to be important components of their anti-hypertensive action.
C57BL/10 female mice were primed to the male specific antigen H-Y, either by grafting with syngeneic male tail skin or by i.p. injection of syngeneic male spleen cells. Primed female spleen cells, either unseparated or filtered through nylon wool to remove most of the B lymphocytes, were then cultured for 5 days in vitro with irradiated syngeneic male spleen cells and assayed against 51Cr-labeled target cells. Both unseparated and nylon wool filtered female cells displayed significant cytotoxic activity restricted to male target cells. Pretreatment of sensitized female cells with antitheta serum and complement just before assay abolished cytotoxic responses. We were unable to demonstrate cell-mediated cytotoxic responses into two nonresponding strains, CBA and B10.A, which fail to reject male isografts. The cytotoxic activity of C57BL/10 female cells was restricted to male target cells histocompatible with C57BL/10 over at least a portion of the major (H-2) histocompatibility complex. We conclude that secondary in vitro cytotoxic responses against the H-Y antigen are mediated by cytotoxic T lymphocytes, and that the H-Y target cell antigen may be specified by the H-2 complex.
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Dapsone (4,4'-diaminodiphenylsulfone [DDS]) was administered intravenously to anesthetized dogs; urine was collected, heparinized venous blood was obtained, and bile was collected from some of the dogs. A constant infusion of inulin was maintained, and isosmotic or hypoosmotic fluids were administered. Dogs were studied under conditions of standardized, increased or decreased urine flow, and before and after plasmapheresis. Plasma, urine, and bile samples were analyzed for DDS and DDS conjugates; the degree of binding of DDS by plasma proteins was also determined. The renal clearances of inulin and DDS were calculated. No monoacetyldapsone (MADDS) was detected in the plasma, and only negligible quantities were found in the urine. Small quantities of DDS and DDS conjugates were detected in the bile in 4 h following the dose. Between 10 and 30% of the administered drug could be identified as DDS plus DDS conjugates in the urine in 8 h after the dose. Renal clearance of unbound DDS was proportional to the urine flow rate, and the clearance ratio of DDS to inulin approached the same maximal value as that for urea. Although the rate of urinary excretion of DDS conjugates was the same in the dog as in man, the rates of excretion of DDS and of DDS plus DDS conjugates were greater in the dog than in man, suggesting that the acetylation of DDS to MADDS by man but not by the dog and the greater degree of plasma protein binding of DDS and MADDS by man account for the longer half-time of disappearance of DDS in man compared to that in the dog.
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