Abstract
Lymphoid cells from normal animals from two genetically alien but isogenic strains of mice or rats elaborated a factor into the medium during in vitro cultivation. Similarly, lymphoid cells from specifically presensitized animals mixed and cultivated with donor-type lymphoid cells, as well as normal or specifically immunized mouse spleen cells exposed to heterologous red blood cell antigens, formed this factor. Culture supernatants of genetically identical lymphoid cells lacked activity. This factor was measured by its ability to induce accumulations of polymorphonuclear cells following injection into the skin of normal hamster hosts. Gentle trypsinization of excised 24 hr cutaneous reactions permitted quantitative estimation of the number of polymorphonuclear cells accumulated and, therefore, of the activity of the factor. The factor present in culture fluids could be defined as a product of antigenic recognition (PAR). PAR was formed only when immunologically competent cells were exposed to cells carrying histocompatibility antigens of recognizable foreignness. This view was based chiefly on the observation that, whereas lymphoid cells from specifically tolerant mice failed to recognize the paralytogen, they did recognize antigens of an unrelated mouse strain. In addition, immunocompetence was of paramount importance, since cocultivation of immunologically incompetent, yet strongly incompatible, rat thymocytes did not result in the formation of PAR. Formation of PAR was observed in very simple media. A source of energy and a suitable culture vessel were found to be the only essential nonimmunological factors for PAR to be elaborated. The presence of inhibitors of glycolysis in the medium during cultivation of mixtures of immunocompetent cells of disparate origin severely inhibited the recognition process. With cell mixtures of the immunological one-way variety, treatment of aggressor cells with inhibitors of glycolysis or of protein synthesis interfered with antigenic recognition, whereas similar treatments of the target cells were without effect. The findings presented sustain the thesis that the elaboration of PAR is a very early event in the immune process.
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- BILLINGHAM R. E., DEFENDIV, SILVERS W. K., STEINMULLER D. Quantitative studies on the induction of tolerance of skin homografts and on runt disease in neonatal rats. J Natl Cancer Inst. 1962 Feb;28:365–435. [PubMed] [Google Scholar]
- Bach F. H., Amos D. B. Hu-1: Major histocompatibility locus in man. Science. 1967 Jun 16;156(3781):1506–1508. doi: 10.1126/science.156.3781.1506. [DOI] [PubMed] [Google Scholar]
- Billingham R. E. The biology of graft-versus-host reactions. Harvey Lect. 1966;62:21–78. [PubMed] [Google Scholar]
- Brent L., Medawar P. Quantitative studies on tissue transplantation immunity. VII. The normal lymphocyte transfer reaction. Proc R Soc Lond B Biol Sci. 1966 Sep 13;165(1000):281–307. doi: 10.1098/rspb.1966.0069. [DOI] [PubMed] [Google Scholar]
- Chase M. W. Delayed sensitivity. Med Clin North Am. 1965 Nov;49(6):1613–1646. doi: 10.1016/s0025-7125(16)33249-7. [DOI] [PubMed] [Google Scholar]
- Dresser D. W., Mitchison N. A. The mechanism of immunological paralysis. Adv Immunol. 1968;8:129–181. doi: 10.1016/s0065-2776(08)60466-6. [DOI] [PubMed] [Google Scholar]
- Dutton R. W. Symposium on in vitro studies of the immune response. II. Significance of the reaction of lymphoid cells to homologous tissue. Bacteriol Rev. 1966 Jun;30(2):397–407. doi: 10.1128/br.30.2.397-407.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Makinodan T., Albright J. F. Proliferative and differentiative manifestations of cellular immune potential. Prog Allergy. 1967;10:1–36. [PubMed] [Google Scholar]
- RAMSEIER H., STREILEIN J. W. HOMOGRAFT SENSITIVITY REACTIONS IN IRRADIATED HAMSTERS. Lancet. 1965 Mar 20;1(7386):622–624. doi: 10.1016/s0140-6736(65)91713-7. [DOI] [PubMed] [Google Scholar]
- Ramseier H., Billingham R. E. Studies on delayed cutaneous inflammatory reactions elicited by inoculation of homologous cells into hamsters' skins. J Exp Med. 1966 Apr 1;123(4):629–656. doi: 10.1084/jem.123.4.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramseier H. Leukotactic factor elaborated by mixtures of genetically dissimilar cells. Science. 1967 Aug 4;157(3788):554–556. doi: 10.1126/science.157.3788.554. [DOI] [PubMed] [Google Scholar]
- Ramseier H., Palm J. Further studies of histocompatibility loci in rats. Transplantation. 1967 Jul;5(4):721–729. doi: 10.1097/00007890-196707000-00014. [DOI] [PubMed] [Google Scholar]
- Silvers W. K., Wilson D. B., Palm J. Mixed leukocyte reactions and histocompatibility in rats. Science. 1967 Feb 10;155(3763):703–704. doi: 10.1126/science.155.3763.703. [DOI] [PubMed] [Google Scholar]
- Uhr J. W., Möller G. Regulatory effect of antibody on the immune response. Adv Immunol. 1968;8:81–127. doi: 10.1016/s0065-2776(08)60465-4. [DOI] [PubMed] [Google Scholar]
- Wilson D. B., Billingham R. E. Lymphocytes and transplantation immunity. Adv Immunol. 1967;7:189–273. doi: 10.1016/s0065-2776(08)60129-7. [DOI] [PubMed] [Google Scholar]
- Wilson D. B. Quantitative studies on the mixed lymphocyte interaction in rats. I. Conditions and parameters of response. J Exp Med. 1967 Oct 1;126(4):625–654. doi: 10.1084/jem.126.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson D. B., Silvers W. K., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. II. Relationship of the proliferative response to the immunologic status of the donors. J Exp Med. 1967 Oct 1;126(4):655–665. doi: 10.1084/jem.126.4.655. [DOI] [PMC free article] [PubMed] [Google Scholar]