Abstract
We have tested the ability of several types of trinitrophenyl (TNP)- labeled Ia+ cells to induce contact hypersensitivity (CS) after intravenous injection. Most labeled cell types (spleen cells, splenic macrophages, various types of peritoneal-exudate cells) not only fail to induce CS after this type of inoculation but, rather, activate T suppressor cells leading to specific immunological tolerance. Occasionally, some of these immunizing cells managed to bypass the T suppressor system and induced CS. In those cases the response was short- lived and could be blocked by concomitant injection of trinitrobenzelsulphonic acid (TNBS), a potent inducer of T suppressor cells. In sharp contrast to these results, TNP-labeled splenic dendritic cells and TNP-labeled peritoneal-exudate cells induced by complete Freund's adjuvant had the following distinctive features: (a) They were always able to sensitize when injected intravenously, and the degree of sensitization they produced was roughly equivalent to that achieved by cutaneous application of picryl chloride, the chemically reactive form of TNP. (b) The response they elicited was long lived (i.e., lasted for greater than 3 wk). (c) Their sensitizing capacity could not be blocked by the concomitant injection of TNBS. (d) They elicited a response that could be adoptively transferred to untreated, normal recipients. These results indicate that the type of cell that first presents antigen to the immune system plays an important, even essential, role in determining the strength and duration of the subsequent immune response. In particular, the results suggest that some special antigen-presenting cells can induce a response that is relatively resistant to host suppressor mechanisms. Evidence that they do so by activating contrasuppressor cells is discussed.
Full Text
The Full Text of this article is available as a PDF (961.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Asherson G. L., Zembala M. Suppression of contact sensitivity by T cells in the mouse. I. Demonstration that suppressor cells act on the effector stage of contact sensitivity; and their induction following in vitro exposure to antigen. Proc R Soc Lond B Biol Sci. 1974 Nov 5;187(1088):329–348. doi: 10.1098/rspb.1974.0078. [DOI] [PubMed] [Google Scholar]
- Askenase P. W., Hayden B. J., Gershon R. K. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med. 1975 Mar 1;141(3):697–702. doi: 10.1084/jem.141.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Celada F. Quantitative studies of the adoptive immunological memory in mice. I. An age-dependent barrier to syngeneic transplantation. J Exp Med. 1966 Jul 1;124(1):1–14. doi: 10.1084/jem.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Claman H. N., Miller S. D., Sy M. S., Moorhead J. W. Suppressive mechanisms involving sensitization and tolerance in contact allergy. Immunol Rev. 1980;50:105–132. doi: 10.1111/j.1600-065x.1980.tb00309.x. [DOI] [PubMed] [Google Scholar]
- DRESSER D. W. A study of the adoptive secondary response to a protein antigen in mice. Proc R Soc Lond B Biol Sci. 1961 Jul 25;154:398–417. doi: 10.1098/rspb.1961.0039. [DOI] [PubMed] [Google Scholar]
- Eardley D. D., Gershon R. K. Feedback induction of suppressor T-cell activity. J Exp Med. 1975 Aug 1;142(2):524–529. doi: 10.1084/jem.142.2.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gershon R. K., Kondo K. Degeneracy of the immune response to sheep red cells. Thymic dependency. Immunology. 1972 Sep;23(3):335–342. [PMC free article] [PubMed] [Google Scholar]
- Greene M. I., Sugimoto M., Benacerraf B. Mechanisms of regulation of cell-mediated immune responses. I. Effect of the route of immunization with TNP-coupled syngeneic cells on the induction and suppression of contact sensitivity to picryl chloride. J Immunol. 1978 May;120(5):1604–1611. [PubMed] [Google Scholar]
- Nussenzweig M. C., Steinman R. M., Gutchinov B., Cohn Z. A. Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes. J Exp Med. 1980 Oct 1;152(4):1070–1084. doi: 10.1084/jem.152.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nussenzweig M. C., Steinman R. M., Unkeless J. C., Witmer M. D., Gutchinov B., Cohn Z. A. Studies of the cell surface of mouse dendritic cells and other leukocytes. J Exp Med. 1981 Jul 1;154(1):168–187. doi: 10.1084/jem.154.1.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ptak W., Rozycka D., Askenase P. W., Gershon R. K. Role of antigen-presenting cells in the development and persistence of contact hypersensitivity. J Exp Med. 1980 Feb 1;151(2):362–375. doi: 10.1084/jem.151.2.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinman R. M. Dendritic cells. Transplantation. 1981 Mar;31(3):151–155. [PubMed] [Google Scholar]
- Steinman R. M., Kaplan G., Witmer M. D., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. J Exp Med. 1979 Jan 1;149(1):1–16. doi: 10.1084/jem.149.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T., Taniguchi M., Takemori T. Properties of primed suppressor T cells and their products. Transplant Rev. 1975;26:106–129. doi: 10.1111/j.1600-065x.1975.tb00177.x. [DOI] [PubMed] [Google Scholar]
- Yamauchi K., Green D. R., Eardley D. D., Murphy D. B., Gershon R. K. Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit. J Exp Med. 1981 Jun 1;153(6):1547–1561. doi: 10.1084/jem.153.6.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeldis J. B., Konigsberg W. H., Richards F. F., Rosenstein R. W. The location and expression of idiotypic determinants in the immunoglobulin variable region--II. Chain location of variable region determinants. Mol Immunol. 1979 Jun;16(6):371–378. doi: 10.1016/0161-5890(79)90102-0. [DOI] [PubMed] [Google Scholar]