scholarly journals CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY

1968 ◽  
Vol 128 (6) ◽  
pp. 1237-1254 ◽  
Author(s):  
Nancy H. Ruddle ◽  
Byron H. Waksman

In the presence of specific antigen, lymph node cells from inbred rats with delayed hypersensitivity to tuberculoprotein, bovine gammaglobulin, and egg albumin produced progressive destruction of monolayers of rat embryo fibroblasts in tissue culture, first apparent at 48 hr and maximal at 72 hr. The effect was specific and did not depend on a genetic difference between the lymph node cells and target cells. It required antigen concentrations equal to or greater than 1.25 µg/ml and lymphocyte: target cell ratios of approximately 10 or 20:1. It could be evaluated both by a plaquing technique and by cell enumeration with an electronic particle counter.

1968 ◽  
Vol 128 (6) ◽  
pp. 1255-1265 ◽  
Author(s):  
Nancy H. Ruddle ◽  
Byron H. Waksman

Damage of rat embryo fibroblasts in the presence of sensitized lymph node cells reacting with specific antigen was shown to be closely correlated with delayed hypersensitivity in the animals from which the lymph node cells were taken. The phenomenon was not correlated with Arthus reactivity. In. animals sensitized with picryl conjugates of ovalbumin or human serum albumin, skin reactivity and the in vitro cytotoxic effect could be elicited only with the homologous conjugate or the protein carrier alone and not with picryl conjugates of heterologous proteins. Lewis rats developed more intense delayed sensitivity than BN rats, and Lewis lymph node cells were correspondingly more effective in producing specific damage of both syngeneic and allogeneic fibroblasts.


1968 ◽  
Vol 128 (6) ◽  
pp. 1267-1279 ◽  
Author(s):  
Nancy H. Ruddle ◽  
Byron H. Waksman

The cytopathic effect of lymph node cells from tuberculin-sensitized rats on rat embryo fibroblasts in the presence of PPD was not enhanced by admixture of normal (nonsensitized) lymph node cells. Preincubation studies showed that this in vitro response is initiated by the reaction of lymphocytes with specific antigen, beginning within 30 min, rather than uptake of antigen by the fibroblasts. The supernatant fluids from suspensions of sensitized cells incubated with PPD for 17 hr or more possessed cytotoxic activity. The target fibroblasts showed a marked increase in acid phosphatase content within 48 hr after the addition of sensitized lymph node cells and antigen.


1958 ◽  
Vol 107 (1) ◽  
pp. 109-124 ◽  
Author(s):  
S. B. Salvin ◽  

Guinea pigs were injected in the footpads with either purified diphtheria toxoid or recrystallized egg albumin in Freund adjuvant without mycobacteria. Each guinea pig was then skin-tested only once with the specific antigen and bled for antibody determination. After injection of the sensitizing antigen, a latent period occurred during which neither sensitivity nor circulating antibody could be detected. A period of delayed sensitivity followed wherein circulating antibody could not be discerned and which could be transferred by lymph node cells. Ultimately, the Arthus type sensitivity developed, accompanied by circulating antibody. The duration and severity of reactions to homologous antigens during the last 2 phases varied with the antigen and with the dose. An increase in the sensitizing dose decreased the duration of the delayed type of allergy, a decrease in the dose prolonged the delayed type. Inclusion of mycobacterium in the sensitizing inoculum tended to introduce delayed sensitivity earlier and delay the onset of Arthus type sensitivity. When specific precipitate in antibody excess was included with the toxoid in the sensitizing dose, the onset of the Arthus phase was hastened. When lymph nodes from a large number of sensitized donors were removed during the latter part of the latent period, recipients of the cells showed a delayed type sensitivity.


1971 ◽  
Vol 134 (5) ◽  
pp. 1144-1154 ◽  
Author(s):  
David G. Tubergen ◽  
Joseph D. Feldman

Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together.


1995 ◽  
Vol 181 (1) ◽  
pp. 393-398 ◽  
Author(s):  
J L Chu ◽  
P Ramos ◽  
A Rosendorff ◽  
J Nikolić-Zugić ◽  
E Lacy ◽  
...  

Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) phenotype. Previous studies have shown that these abnormal cells are capable of inducing redirected lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL) has recently been shown to be partly responsible for T cell-mediated cytotoxicity, lymph node cells from lpr and gld mice were examined for the expression of FasL mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr and gld mice had a striking increase in the level of expression of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive up-regulation of FasL which, most likely, results from repetitive exposure to (self) antigen. This phenomenon could explain the lpr-induced wasting syndrome observed when lpr bone marrow-derived cells are adoptively transferred to wild-type recipients.


1977 ◽  
Vol 145 (2) ◽  
pp. 302-313 ◽  
Author(s):  
E W Lamon ◽  
M W Shaw ◽  
S Goodson ◽  
B Lidin ◽  
A S Walia ◽  
...  

Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was evaluated in terms of the differential ability of IgG and IgM from MSV regressor animals to induce cytotoxicity by lymphocytes from lymph node, spleen, and thymus. The cell-mediated cytotoxicity induced by both IgM and IgG was specific for target possessing the appropriate virally determined cell surface antigen(s). IgM induced cytotoxicity by lymphocytes from all the organs tested. However, differences in magnitude and efficiency were revealed. Lymph node cells and thymocytes were most efficient against IgM-coated target cells. Against IgG-sensitized target cells, spleen and lymph node cells were about equally active, but thymocytes were inactive. Cortisone treatment of the donors of effector cells revealed that the cortisone resistant subpopulation of thymocytes, 2 days after cortisone injection, exhibited an increased cytotoxicity against target cells treated with unfractionated antiserum and its IgM fraction. This subpopulation of thymocytes was also cytotoxic against IgG-coated target cells. At 12 days after cortisone injection, the repopulated thymus showed little change in activity, compared to control thymus, against antibody-coated target cells.


1967 ◽  
Vol 125 (3) ◽  
pp. 511-526 ◽  
Author(s):  
Ira Green ◽  
Pierre Vassalli ◽  
Victor Nussenzweig ◽  
Baruj Benacerraf

A combination of double immunofluorescent technique and radioautographic localization of radioactive antigens was used to investigate the question whether single antibody-producing cells can make antibodies of more than one specificity after immunization with antigens bearing more than one determinant. When guinea pig γ2-globulins, containing the F(ab')2 and Fc determinants, were used to immunize rabbits, a small percentage of cells (3.7%) were stained with both the anti-F(ab')2 and anti-Fc reagents. These results were shown to be due to the lack of absolute specificity of the detecting antigen and antibody reagents which can be obtained for use in this system. However, when immunological systems such as hapten-protein conjugates were used, and where completely specific antigen and antibody reagents could be prepared, the results were unequivocal. The individual lymph node cells from rabbits or guinea pigs immunized with hapten-protein conjugates produced antibodies against the hapten or antibodies against the antigenic determinants of the carrier molecule, never antibodies against both specificities.


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