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Biomedical subjects

J A Bash

Publications and source records attributed to J A Bash.

36 records · Page 2Linked to original sources
PubMed1981

Inhibition of macrophage-induced tumor cell cytostasis and cytolysis by tumor-promoting phorbol diesters.

The effects of 3 tumor-promoting phorbol diesters and the corresponding inactive polyol phorbol on cytostatic and cytolytic activities of activated murine peritoneal macrophages toward target tumor cells derived from skin cells of the same species were examined. In both cases the diesters, without showing concurrent toxicity, considerably suppressed in dose-related fashion, the activity of the macrophages at concentrations active in promotion in vivo, being active even in nanogram quantities. The order of activity among different diesters for cytostasis or cytolysis was the same as that observed toward tumor promotion in mouse skin. The non-promoter phorbol was inactive in all instances. These findings concur with proposals for an important role for abrogation of normal antitumor defense mechanisms in promotion of mouse skin carcinogenesis by active phorbol diesters.

Animals↗
PubMed1979

Immunoregulation of Heymann's nephritis. I. Induction of suppressor cells.

Pretreatment of Lewis rats with a series of injections of a renal tubular antigen (RTA) in IFA prevented induction of Heymann's nephritis (HN) when the rats were challenged with RTA in FCA. This absence of disease was confirmed by immunofluorescent staining for rat IgG and histologic examination of the kidneys as well as by lack of development of significant proteinuria. Passive transfer of spleen and lymph node cells from rats receiving such pretreatment into syngeneic recipients prevented induction of HN when these recipients were challenged with RTA in FCA. Passive transfer of serum obtained from pretreated rats was without effect. These results suggest that one of the mechanisms involved in preventing HN by this pretreatment regimen was the induction of suppressor cells. The results of spleen cell transformation indicated that the suppressor cells were specific for RTA as the immune response to a second antigen, PPD, was unaffected. When rats already had active early HN, the diseas course was unaffected by transfer of suppressor cells.

Animals↗
PubMed1976

The suppressive effect of immunization on the proliferative responses of rat T cells in vitro. II. Abrogation of antigen-induced suppression by selective cytotoxic agents.

Rats given large i.v. doses of ovalbumin or sheep erythrocytes manifest suppressed spleen cell responses (3H-thymidine incorporation) to PHA within hours. Removal of glass wool-adherent cells totally restores responsiveness to that of normal nonadherent spleen cell cultures. Carrageenan, selectively toxic for macrophages, partially restores responses of antigen-suppressed spleen cells in culture, suggesting a supportive role for macrophages in the suppression phenomenon. Treatment of donors with low doses of cyclophosphamide (20 to 50 mg/kg) at the time of antigen injection abrogates the ability of their spleen cells to suppress the responses of normal cells to PHA. The low dose of cyclophosphamide required indicates a target other than the B cell or macrophage and suggests the possibility that cyclophosphamide eliminates the suppressor T cell component of the macrophage-T cell complex.

Animals↗
PubMed1975

Kinetic study of T lymphocytes after sensitization against soluble antigen. III. Potentiation and suppression of the PHA response by antigen-activated lymphocytes of low density.

Lymph node cells of ovalbumin-sensitized rats were separated on the basis of buoyant density into fractions reciprocally enriched in cells responsive to ovalbumin or phytohemagglutinin (PHA). Recombination of high density and low density fractions in varying proportions resulted in potentiation or suppression of the DNA synthetic response to PHA in culture. The response of cultures containing equal numbers of high and low density cells was markedly greater than the sum of the two populations stimulated separately. However, when decreasing numbers of low density cells were cultured with a constant number of high density cells, profound suppression was observed.

Animals↗
PubMed1975

Separation of T cell subpopulations capable of DNA synthesis, lymphotoxin release, and regulation of antigen and phytohemagglutinin responses on the basis of density and adherence properties.

T memory cells specifically responsive to ovalbumin and performing the diverse functions of DNA synthesis, lymphotoxin release, and regulation can be isolated in enriched numbers in the most buoyant fractions (A+B) of bovine serum albumin gradients on day 9 after sensitization. At least 20-30% of these cells are capable of mounting a blastogenic response to ovalbumin. A+B cells responding to ovalbumin with DNA synthesis have adherent properties and are further enriched on passage through glass wool. The subpopulations capable of entering into blastogenesis and DNA synthesis and of lymphotoxin release are unresponsive to T mitogens. A+B cells are capable of either potentiating or suppressing DNA synthetic responses to both phytohemagglutinin and antigen when added to 5 X 10(5) D cells in different proportions. Potentiation or suppression of phytohemagglutinin responses were observed with 1 X 10(5) A+B cells, and total suppression was observed with A+B in the range of 4 X 10(3) to 2 X 10(4). The response to antigen was sometimes inhibited in the same cell combinations that gave a potentiated response to phytohemagglutinin and vice versa. Regulatory cells in this system were not macrophages since their effect was not mimicked by addition of peritoneal macrophages, and ablation of macrophages by carrageenan affected neither the potentiation nor suppression.

Animals↗
PubMed1975

The suppressive effect of immunization on the proliferative responses of rat T cells in vitro.

DNA synthesis (3H-thymidine incorporation) of DA rat spleen and lymph node cells cultured with PHA or (DA x Lewis)F1 lymph node cells was profoundly inhibited by pretreatment with large i.v. doses of antigen (greater than 100 mg OA or greater than 10(10) SRBC) 24 hr before culture. This effect, seen as early as 3 to 6 hr after antigen administration, had disappeared within 7 days. Similar depressed spleen cell responses were seen 9 days after footpad injection of 200 mug OA in complete adjuvant. Lymph node responses showed a similar inhibition only in the presence of specific antigen in culture. In all experiments in which antigen administration resulted in decreased responses, removal of glass wool adherent cells restored responsiveness to normal. The failure of purified macrophages to reestablish inhibition favored the interpretation that an adherent suppressor cell distinct from the macrophage is activated by antigen in vivo to regulate T cell responses in vitro.

Animals↗
PubMedDate not supplied

Cellular immunosenescence in F344 rats: decline in responsiveness to phytohemagglutinin involves changes in both T cells and macrophages.

Spleen cells from F344 male rats showed decreased DNA synthetic responsiveness [( 3H]thymidine incorporation) with age to the T cell mitogen phytohemagglutinin (PHA). Decreased proliferative responses were associated with decreased production of interleukin-2 (IL-2) and could be partially restored by providing exogenous IL-2. Responses of spleen cells from aged rats could also be enhanced by removal of Sephadex G-10 adherent cells. Furthermore, co-culture of adherent cell-containing spleen cells from aged rats with nonadherent spleen cells from young rats resulted in suppression of responses. Purified peritoneal exudate macrophages (PEM) from aged rats showed potent regulatory effects on PHA responses of young and old nonadherent spleen cells resulting in suppression above 2.5% macrophage/nonadherent spleen cell ratios. PEM from young rats enhanced the response of young T cells but failed to affect the response of aged T cells. T cell proliferation in the presence of prostaglandin (PGE1) showed age-dependent differences in regulation such that at 10(-6) to 10(-7) M young responses were enhanced and old responses were suppressed. These results suggest that decreased responsiveness of T cells to PHA with age is a complex phenomenon involving changes in both production of regulatory mediators by T cells (IL-2) and macrophages (PGE) as well as changes in T cell responsiveness to these signals.

Aging↗