scholarly journals HAPTEN CARRIER RELATIONSHIPS IN THE DNP-PLL·FOREIGN ALBUMIN COMPLEX SYSTEM: INDUCTION OF TOLERANCE AND STIMULATION OF CELLS IN VITRO

1968 ◽  
Vol 127 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Ira Green ◽  
William E. Paul ◽  
Baruj Benacerraf

Genetic nonresponder guinea pigs made tolerant to BSA and then immunized with DNP-PLL·BSA failed to make anti-DNP-PLL antibodies. Thus, tolerance to a carrier protein renders animals unresponsive to the hapten which it bears. The addition in vitro of DNP-PLL or DNP-GL to lymph node cell cultures derived from genetic responder animals immunized with these materials led to a significant stimulation of 3H-thymidine incorporation into DNA. However, the addition of DNP-PLL or DNP-GL to lymph node cell cultures from nonresponder animals immunized with these materials failed to produce any stimulation of DNA synthesis. Furthermore, the addition of DNP-PLL to lymph node cell cultures from nonresponder animals immunized with DNP-PLL·BSA or DNP-PLL·OVA also failed to stimulate cell proliferation in spite of the fact that the lymph node cells of these animals were producing anti-DNP-PLL antibodies. The above facts suggest that the function of the PLL gene product is to act at an early crucial step in the immune mechanism to form an antigen-inducer complex. The specificity of this early step may be of a simple order and different than that of the antibody which is later produced in the immune response.

1969 ◽  
Vol 129 (2) ◽  
pp. 295-313 ◽  
Author(s):  
John Foerster ◽  
Jean-Pierre Lamelin ◽  
Ira Green ◽  
Baruj Benacerraf

Rabbit anti-guinea pig lymphocyte serum is an efficient stimulus of the synthesis of DNA by guinea pig lymph node cells in vitro. The ability of ALS to stimulate lymphocytes is characterized by its lack of dependence on prior sensitization, the magnitude of the response it elicits, and the stimulation of all sensitive lymph node cells simultaneously within a very narrow range of ALS concentrations. In contrast to this homogeneous response to ALS, the stimulation of lymph node cells by antigen proceeds in graded fashion over a wide range of concentrations, thus reflecting the heterogeneity of the response of sensitized cells to antigen. PHA gives a response which is intermediate between that of ALS and antigen. ALS appears to have specificity for membrane determinants shared by lymphocytes but not found on other tissues. This specificity does not involve cell-bound gamma globulin. The serum activity mediating lymphocyte stimulation as well as cytotoxicity is readily removed by absorption with lymph node cells.


1969 ◽  
Vol 130 (5) ◽  
pp. 1031-1045 ◽  
Author(s):  
Stuart F. Schlossman ◽  
Judith Herman ◽  
Arieh Yaron

Studies of the immunochemical specificity of antigen-induced thymidine-2-14C incorporation in lymph node cells obtained from animals immunized to a series of closely related α-DNP-oligolysines, ϵ-DNP-oligolysines, and oligolysines have shown that the sensitized cell exhibits an extraordinary degree of specificity for antigen. The sensitized cell is maximally stimulated by the homologous immunizing antigen and can discriminate among compounds which differ from one another only in the position of a dinitrophenyl group or D-lysine residue on an identical oligolysine backbone. These studies support the view that the immunogen is not degraded prior to the induction of the immune response, and that the majority of cells produced as a consequence of immunization have stereospecific antigen receptors for the DNP-oligolysine used to induce the response; a smaller and more variably sized population of cells is produced with receptors specific for the oligolysine portion of the immunizing antigen. When specifically sensitized lymph node cell cultures are stimulated in vitro by heterologous DNP-oligolysines, the oligolysine- and not the DNP-oligolysine-sensitive population of cells appears to play a crucial role in the specificity of such cross-reactions. It is concluded from these studies that the antigen receptor on the sensitized lymph node cell differs in both kind and degree from conventional antibody. The chemical nature of the receptor and the means by which this receptor reacts with antigen to initiate the biosynthetic or proliferative cellular immune response still remain undefined.


1975 ◽  
Vol 142 (3) ◽  
pp. 600-610 ◽  
Author(s):  
K U Hartmann ◽  
V A Bokisch

Addition of isolated B3b to murine lymph node cell cultures induced increased DNA synthesis. The stimulation is dependent on the dose of C3b added and is potentiated by fetal calf serum present in the medium. Isolated C3 is less stimulatory than C3b; C3a and C3c had no effect on DNA synthesis in these cultures. 10-20% large immunoglobulin containing blastlike cells developed in lymph node cell cultures stimulated by 50 mug C3b in the presence of 3% fetal calf serum. The stimulation by C3b was observed in cultures of lymph node and spleen cells of several mouse strains including C3H/HeJ and congenitally thymus-deficient (nu/nu) mice. The results suggest that B lymphocytes are the main target of the stimulatory effect of C3b. Two mechanisms which may be involved in the stimulation of lymphocytes by C3b are discussed: (a) cross-linking of receptors on the cell surface or between cells, and (b) the binding of C3b to receptors of B lymphocytes and the formation of the complement enzyme C3bB. The results are compatible with the suggestion that activation of C3 is part of the events triggering the B lymphocytes.


1971 ◽  
Vol 133 (2) ◽  
pp. 202-215 ◽  
Author(s):  
Robert C. Bast ◽  
Blanche A. Simpson ◽  
Harold F. Dvorak

Antigen-mediated stimulation of thymidine incorporation was demonstrated in lymph node cells from guinea pigs immunized with 100 µg human serum albumin in either Freund's incomplete or Freund's complete adjuvant. Animals receiving HSA in IFA exhibited both cutaneous basophil (Jones-Mote) hypersensitivity and lymphocyte stimulation at 1, but not at 6 wk after immunization. Significant stimulation required ≥ 10 µg HSA/ml of culture. Sensitization with HSA in CFA produced delayed hypersensitivity and permitted lymphocyte stimulation at both 1 and 6 wk. Stimulation was observed with as little as 0.1 µg HSA/ml at the later interval. Administration of 5 mg HSA intravenously at the time of sensitization with 100 µg HSA in IFA reduced but did not eliminate both CBH and lymphocyte stimulation at 1 wk. Antigen-specific inhibition of macrophage migration could be demonstrated with exudates from animals immunized with HSA in CFA, but not with HSA in IFA at 3 wk after sensitization. HSA was cleared from depots of CFA and IFA at similar rates, but significantly more antigen appeared in the plasma and subsequently in the draining lymph nodes following administration in IFA. Conversely, accumulated antigen disappeared more rapidly following CFA immunization.


2006 ◽  
Vol 13 (2) ◽  
pp. 289-296 ◽  
Author(s):  
Corey A. Amlong ◽  
Dean T. Nardelli ◽  
Sara Heil Peterson ◽  
Thomas F. Warner ◽  
Steven M. Callister ◽  
...  

ABSTRACT We showed previously that interleukin-17 (IL-17) plays a significant role in the induction of arthritis associated with Borrelia vaccination and challenge. Little information, however, is available about the chain of immunologic events that leads to the release of IL-17. The production of IL-17 has been linked to stimulation of memory cells by IL-15. Therefore, we hypothesized that IL-15 is involved in the induction of arthritis associated with Borrelia vaccination and infection of mice. Here we present evidence that treatment of Borrelia-vaccinated and -infected mice with anti-IL-15 antibody prevents swelling of the hind paws. More importantly, both anti-IL-15 antibody- and recombinant IL-15 receptor alpha-treated Borrelia-vaccinated and -infected mice were free of major histopathologic indications of arthritis, including hyperplasia, hypertrophy, and vilus formation of the synovium. Similarly, the synovial space and perisynovium were free of inflammatory cells. By contrast, the synovium of nontreated Borrelia-vaccinated and -infected mice had overt hyperplasia, hypertrophy, and vilus formation. Moreover, the synovial space and perisynovium were infiltrated with neutrophils, macrophages, and lymphocytes. Finally, we show that recombinant IL-15 stimulates the release of IL-17 from lymph node cells obtained near the arthritic site. These results suggest that IL-15 plays a major role in orchestrating IL-17 induction of arthritis associated with Borrelia-vaccinated and -infected mice.


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