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Biomedical subjects

G Doria

Publications and source records attributed to G Doria.

At least 19 recordsLinked to original sources
PubMed1992

Effect of in vivo hyperthermia on thymocyte maturation and selection.

Two-month-old male mice were exposed to whole-body hyperthermic treatment in a circulating water bath. After 1 h exposure to 41 degrees C, mice were kept at room temperature for 24, 48, 72, and 96 h before thymus examination. The total thymocyte number progressively decreased after 24 and 48 h, reached a minimum value at 72 h, and returned to almost normal value after 96 h. Similar changes occurred in the CD4+CD8+ cell subset. Conversely, the percentage of CD4-CD8- cells rose to a maximum at 48 h and then declined to normal value at 96 h. The percentage of CD4-CD8+ and CD4+CD8- cell subsets increased to a maximum at 48 h and then declined to normal value at 96 h. These variations in single positive cell subsets correlated well with similar changes in the thymocyte mitotic response to concanavalin A. The observed effects on thymocytes were heat dose dependent, and suggest that hyperthermia induces the development of the most primitive thymocytes and positively selects mature T cells with high mitotic responsiveness. It is proposed that heat shock proteins might be involved in the hyperthermia-induced alterations of thymocyte maturation and selection.

Animals↗
PubMed1992

Effect of synthetic thymic humoral factor (THF-gamma 2) on T cell activities in immunodeficient ageing mice.

Immunodeficient ageing (C57BL/10 x DBA/2)F1 mice were treated by a single injection of synthetic thymic hormones and 4 days later their thymus and spleen cells were assayed in vitro for T cell activities. A few nanograms of THF-gamma 2 were found to raise the frequency of mitogen-responsive T cells in thymus and spleen cell populations as well as the frequency of cytokine-producing splenic T cells, up to the levels observed in young mice. Moreover, injection of THF-gamma 2 was found to restore T cell growth factor (TCGF) production by mitogen-stimulated spleen cells. Also, the helper activity of spleen cells was enhanced by this treatment and increased with increasing the THF-gamma 2 dose over a wide range. Similarly, the effects of thymopentin and thymosin-alpha 1 on T helper cell activity increased with increasing the injected dose, but the efficiencies of THF-gamma 2 and thymopentin were, respectively, 400-fold and eight-fold greater than that of thymosin-alpha 1.

Aging↗
PubMed1978

Time and antigen dose-dependent variations of IgM antibody affinity.

Affinity of IgM antibodies elicited in mice by a single injection of dinitrophenylated dextran was measured by equilibrium dialysis. Maturation of affinity was found to occur with time, the rate of increase being higher after larger antigen doses. Maturation was followed by a decrease of affinity with time, the fall being more pronounced after lower antigen doses. These findings are more in line with the theory of antigen-induced diversity rather than with the maturation theory.

Animals↗
PubMed1978

Radiosensitivity of the helper cell function.

The helper function of T cells primed and irradiated in vivo was tested in vitro by the Mishell-Dutton technique. Spleen cells from mice carrier-primed with HRBC and exposed to 50 to 2000 rads of x-radiation were assayed for their ability to help syngeneic normal spleen cells to mount an in vitro anti-hapten antibody response after stimulation with the conjugate TNP-HRBC. The anti-TNP response was evaluated by the Jerne technique. The helper activity was titrated by adding graded numbers of carrier-primed spleen cells to a constant number of normal spleen cells. The slope of the initial linear portion of the response-cell dose titration curve was taken as an estimated of the helper activity and found to decrease with increasing the x-ray dose. The curve describing the remaining helper activity as a function of the radiation dose shows the presence of two components, one radiosensitive, the other, radioresistant. This suggests the existence either of helper cells at different stages of activation or of two cell subpopulations participating in the helper function.

Animals↗
PubMed1978

Age-dependent variations of antibody avidity.

Age-dependent variations of antibody avidity were studied in the C3HeB/FeJ mouse. Spleen cells from donors of different ages (10--720 days) were transferred and stimulated with TNP-HRBC in lethally irradiated syngenic recipients. The anti-TNP antibody response of the donor cells was estimated from the number of direct PFC per recipient spleen by the Jerne technique with TNP-SRBC. Avidity of the antibodies secreted by PFC was evaluated from the amount of added TNP-BSA that inhibited 50% of the anti-TNP PFC. Under these experimental conditions allowing the exclusion of any influence of the donor milieu during the immune response, age-dependent variations of the antibody response and avidity could be attributed to changes in the donor spleen cell population. Avidity was found to increase with the response and to vary parabolically with age. After appropriate correction of the number of PFC to make it independent from age, avidity values were fitted by a multiple curvilinear regression in which the independent variables playing a significant role were the corrected number of PFC in its linear term and the age in its linear and quadratic terms. From comparison of the standard coefficients of this regression, the observed variations of avidity could be attributed in part (82%) to the response and in part (18%) to the age. For any value of response, avidity increased 15-fold from day 10 to reach a maximum at day 110 and then declined 5-fold at the age of 720 days. Heterogeneity of avidity also changed parabolically with age as high avidity classes were present in adulthood and absent at 10 and 720 days.

Aging↗
PubMed1978

Secretion rate independent evaluation of IgM antibody avidity at the level of single immunocytes.

The hemolytic plaque inhibition assay has been performed on spleen cells from mice immunized with TNP-HRBC to evaluate avidity of anti-TNP IgM antibodies. At different times after immunization direct plaques were inhibited by soluble TNP-EACA, TNP61-BGG, or anti-mu antiserum. Analysis of the inhibition data provided independent estimates of antibody avidity and secretion rate. Avidity was found to increase with time, to reach a maximum when the antibody response attained the peak value, and then to decline as the response was waning. There was a decrease followed by increase of the secretion rate concomitant with the rise and fall of the antibody response and avidity.

Aminocaproic Acid↗
PubMed1978

In vitro immune response of spleen cells from mice genetically selected for high or low antibody production.

The aim of this study was the identification of the cell type in which genes selected for high or low response to SRBC express their functions. Spleen cells from high (H) and low (L) responder mice were immunized with SRBC in the Mishell and Dutton system. An antibody response of different magnitude was found in cultures of H and L spleen cells, the difference being at least as great as that observed in vivo. This finding under experimental conditions allowing the exclusion of any influence of the animal milieu during the immune response, suggest macrophages, B, and T lymphocytes as possible target cells of gene action. In vitro cell separation and recombination experiments in which spleen cells were immunized with SRBC, TNP-LPS, or TNP-HRBC indicate that the genetic differences between H and L responders brought about by selective breeding are expressed in lymphocytes to greater extent than in macrophages. The role of histoincompatibility in the recombination experiments in unlikely but cannot be excluded. Among lymphocytes, B cells but not helper T cells were found more responsive in cultures of spleen cells from H than from L mice.

Animals↗
PubMed1977

Enhanced antibody affinity in sublethally irradiated mice and bone marrow chimeras.

Sublethally irradiated mice primed with dinitrophenyl (Dnp)-keyhole limpet hemocyanin immediately after irradiation or 30 days later and subsequently boosted with a second injection of antigen displayed a secondary response to Dnp characterized by antibody affinity greater than that in unirradiated controls. Also, in radiation chimeras primed with Dnp-keyhole limpet hemocyanin 120 days after syngeneic or allogeneic bone marrow transplantation the antibodies against Dnp produced after boosting were of higher affinity than the antibodies raised in normal mice. These findings are tentatively attributed to lack of suppressor thymus-derived lymphocytes (T cells) in sublethally irradiated mice and bone marrow chimeras, in which the enhanced ability to produce antibodies of high affinity may compensate for quantitative defects of the immune system.

Animals↗
PubMed1977

Effects of whole-body irradiation on antibody affinity.

Mice exposed to a sublethal dose of X-rays were immunized with alum-precipitated DNP-KLH (dinitrophenyl-keyhole limpet haemocyanin) and B. pertussis either before or after irradiation. The primary anti-DNP antibody response was evaluated during 8 weeks after immunization by the equilibrium dialysis technique using ammonium sulphate- precipitated serum globulins and the ligand 3H-labelled xi-DNP-L-Lysine. The serum concentrations of antibody sites in mice immunized 1-5 days before or 2 h-8 weeks after 450 rad were below the values in unirradiated controls at all bleeding times. Antibody affinity, however, was found to be up to 20 fold higher in irradiated mice than in control mice when antigen was injected before, or 3-8 weeks after, irradiation. Spleen cells from mice exposed to 450 rad 1-9 weeks before killing were stimulated in vitro with PHA, ConA, or LPS. Recovery profiles of mitotic responsiveness suggest that enhancement of antibody affinity in irradiated mice could result from relative lack of suppressor T Cells.

Animals↗
PubMed1976

Cell selection in the thymus of mice treated with escherichia coli lipopolysaccharide (LPS).

The present data indicate that injection of LPS induces a decrease in thymus weight with selection of thymocytes more efficient in killer and helper activities. It has been reported (12) that two T-cell types may cooperate in the GVH reaction: the effector T1 and the amplifier T2. The maturation from T1 to T2 occurs mainly in the periphery, whereas immature cortex thymocytes differentiate to T1 within the thymus (13). Our results, showing an LPS-dependent enhancement of thymocyte killing activity, suggest that LPS selects thymocytes mostly of the T1 type. LPS-treated thymocytes are more efficient in the reconstitution of the anti-SRBC response. These data can be explained considering that LPS, like cortisone (14), enriches the thymus with more immunocompetent helper cells. Alternatively it may be suggested that LPS selects in the thymus cell populations characterized by high proliferative activity. Unpublished observations showing that LPS-treatment in vivo increases the in vitro response of thymocytes to Con-A are consistent with this interpretation.

Animals↗