Abstract
The immune response of C57BL mice to a DBA/2 tumor allograft has been assessed in two assays of cell-mediated immunity, the in vitro lysis of 51Cr-labeled target cells and the antigen-mediated inhibition of macrophage migration. Both assays were shown to be measuring a T-cell-mediated reaction. Three types of experiments suggested that distinct subpopulations of T cells mediate these reactions. The tissue distributions of these activities was distinctive; both activities were present in spleens from i.p. immunized mice, but only macrophage migration inhibition activity was found in the peripheral lymph nodes (PLN) of such mice. Adoptive transfer of immune spleen cells into irradiated syngeneic recipients revealed that while a substantial amount of migration inhibition activity could subsequently be found in PLN, cytotoxic activity was found predominantly in the spleens of these adoptive hosts. Velocity sedimentation analysis of immune cells 14 days after i.p. immunization indicated that while the majority of cytotoxic activity was associated with small and medium lymphocytes, the majority of migration inhibition activity was associated with medium and large lymphocytes. In addition, normal spleen cells were fractionated by velocity sedimentation immediately before allosensitization in vitro. Subsequent analysis of the sensitized fractions revealed that the activity profiles for cytotoxicity and macrophage migration inhibition were not coincident. The implications of these observations are discussed.
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- Boyle W. An extension of the 51Cr-release assay for the estimation of mouse cytotoxins. Transplantation. 1968 Sep;6(6):761–764. doi: 10.1097/00007890-196809000-00002. [DOI] [PubMed] [Google Scholar]
- Brunner K. T., Mauel J., Rudolf H., Chapuis B. Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology. 1970 Apr;18(4):501–515. [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Asofsky R. Synergy among lymphoid cells mediating the graft-versus-host response. 3. Evidence for interaction between two types of thymus-derived cells. J Exp Med. 1972 Apr 1;135(4):764–779. doi: 10.1084/jem.135.4.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Canty T. G., Wunderlich J. R., Fletcher F. Qualitative and quantitative studies of cytotoxic immune cells. J Immunol. 1971 Jan;106(1):200–208. [PubMed] [Google Scholar]
- Canty T. G., Wunderlich J. R. Quantitative in vitro assay of cytotoxic cellular immunity. J Natl Cancer Inst. 1970 Oct;45(4):761–772. [PubMed] [Google Scholar]
- Claman H. N., Chaperon E. A. Immunologic complementation between thymus and marrow cells--a model for the two-cell theory of immunocompetence. Transplant Rev. 1969;1:92–113. doi: 10.1111/j.1600-065x.1969.tb00137.x. [DOI] [PubMed] [Google Scholar]
- Cohen L., Howe M. L. Synergism between subpopulations of thymus-derived cells mediating the proliferative and effector phases of the mixed lymphocyte reaction. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2707–2710. doi: 10.1073/pnas.70.9.2707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham A. J. A method of increased sensitivity for detecting single antibody-forming cells. Nature. 1965 Sep 4;207(5001):1106–1107. doi: 10.1038/2071106a0. [DOI] [PubMed] [Google Scholar]
- DAVID J. R., AL-ASKARI S., LAWRENCE H. S., THOMAS L. DELAYED HYPERSENSITIVITY IN VITRO. I. THE SPECIFICITY OF INHIBITION OF CELL MIGRATION BY ANTIGENS. J Immunol. 1964 Aug;93:264–273. [PubMed] [Google Scholar]
- DUNN T. B., POTTER M. A transplantable mast-cell neoplasm in the mouse. J Natl Cancer Inst. 1957 Apr;18(4):587–601. [PubMed] [Google Scholar]
- Davies A. J. The thymus and the cellular basis of immunity. Transplant Rev. 1969;1:43–91. doi: 10.1111/j.1600-065x.1969.tb00136.x. [DOI] [PubMed] [Google Scholar]
- Evans R., Alexander P. Mechanism of immunologically specific killing of tumour cells by macrophages. Nature. 1972 Mar 24;236(5343):168–170. doi: 10.1038/236168a0. [DOI] [PubMed] [Google Scholar]
- Evans R., Grant C. K. Role of macrophages in tumour immunity. 3. Co-operation between macrophages and lymphoid factors in an in vitro allograft situation. Immunology. 1972 Nov;23(5):677–687. [PMC free article] [PubMed] [Google Scholar]
- Feldmann M., Easten A. The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response. J Exp Med. 1971 Jul 1;134(1):103–119. doi: 10.1084/jem.134.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frost P., Lance E. M. Abrogation of lymphocyte trapping by ascitic tumours. Nature. 1973 Nov 9;246(5428):101–103. doi: 10.1038/246101a0. [DOI] [PubMed] [Google Scholar]
- GORER P. A. Some recent work on tumor immunity. Adv Cancer Res. 1956;4:149–186. doi: 10.1016/s0065-230x(08)60724-1. [DOI] [PubMed] [Google Scholar]
- GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
- Golub E. S. Brain-associated theta antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells. Cell Immunol. 1971 Aug;2(4):353–361. doi: 10.1016/0008-8749(71)90070-0. [DOI] [PubMed] [Google Scholar]
- Gorczynski R. M. Evidence for in vivo protection against murine-sarcoma virus-induced tumors by T lymphocytes from immune animals. J Immunol. 1974 Feb;112(2):533–539. [PubMed] [Google Scholar]
- Gorczynski R. M. Immunity to murine sarcoma virus-inducted tumors. I. Specific T lymphocytes active in macrophage migration inhibition and lymphocyte transformation. J Immunol. 1974 May;112(5):1815–1825. [PubMed] [Google Scholar]
- Gorczynski R. M. Immunity to murine sarcoma virus-inducted tumors. II. Suppression of T cell-mediated immunity by cells from progressor animals. J Immunol. 1974 May;112(5):1826–1838. [PubMed] [Google Scholar]
- Gordon J., Yu H. Relationship of T cells involved in cell-mediated immunity and antibody synthesis. Nat New Biol. 1973 Jul 4;244(131):21–22. doi: 10.1038/newbio244021a0. [DOI] [PubMed] [Google Scholar]
- Grant C. K., Currie G. A., Alexander P. Thymocytes from mice immunized against an allograft render bone-marrow cells specifically cytotoxic. J Exp Med. 1972 Jan;135(1):150–164. doi: 10.1084/jem.135.1.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greaves M., Janossy G. Elicitation of selective T and B lymphocyte responses by cell surface binding ligands. Transplant Rev. 1972;11:87–130. doi: 10.1111/j.1600-065x.1972.tb00047.x. [DOI] [PubMed] [Google Scholar]
- JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
- Kano S., Bloom B. R., Howe M. L. Enumeration of activated thymus-derived lymphocytes by the virus plaque assay. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2299–2303. doi: 10.1073/pnas.70.8.2299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lance E. M., Taub R. N. Segregation of lymphocyte populations through differential migration. Nature. 1969 Mar 1;221(5183):841–843. doi: 10.1038/221841a0. [DOI] [PubMed] [Google Scholar]
- Lohmann-Matthes M. L., Schipper H., Fischer H. Macrophage-mediated cytotoxicity against allogeneic target cells in vitro. Eur J Immunol. 1972 Feb;2(1):45–49. doi: 10.1002/eji.1830020110. [DOI] [PubMed] [Google Scholar]
- MacDonald H. R., Phillips R. A., Miller R. G. Allograft immunity in the mouse. 1. Quantitation and specificity of cytotoxic effector cells after in vitro sensitization. J Immunol. 1973 Aug;111(2):565–574. [PubMed] [Google Scholar]
- MacLennan I. C., Loewi G., Howard A. A human serum immunoglobulin with specificity for certain homologous target cells, which induces target cell damage by normal human lymphocytes. Immunology. 1969 Dec;17(6):897–910. [PMC free article] [PubMed] [Google Scholar]
- Miller H. C., Cudkowicz G. Density gradient separation of marrow cells restricted for antibody class. Science. 1971 Mar 5;171(3974):913–915. doi: 10.1126/science.171.3974.913. [DOI] [PubMed] [Google Scholar]
- Miller J. F., Mitchell G. F. Thymus and antigen-reactive cells. Transplant Rev. 1969;1:3–42. doi: 10.1111/j.1600-065x.1969.tb00135.x. [DOI] [PubMed] [Google Scholar]
- Miller R. G., Phillips R. A. Sedimentation analysis of the cells in mice required to initiate an in vivo immune response to sheep erythrocytes. Proc Soc Exp Biol Med. 1970 Oct;135(1):63–67. doi: 10.3181/00379727-135-34988. [DOI] [PubMed] [Google Scholar]
- Miller R. G., Phillips R. A. Separation of cells by velocity sedimentation. J Cell Physiol. 1969 Jun;73(3):191–201. doi: 10.1002/jcp.1040730305. [DOI] [PubMed] [Google Scholar]
- Mäkelä O., Cross A. M. The diversity and specialization of immunocytes. Prog Allergy. 1970;14:145–207. doi: 10.1159/000289379. [DOI] [PubMed] [Google Scholar]
- Nordin A. A., Cosenza H., Sell S. Immunoglobulin classes of antibody-forming cells in mice. II. Class restriction of plaque-forming cells demonstrated by replica plating. J Immunol. 1970 Feb;104(2):495–501. [PubMed] [Google Scholar]
- Nossal G. J., Bussard A. E., Lewis H., Mazie J. C. In vitro stimulation of antibody formation by peritoneal cells. I. Plaque technique of high sensitivity enabling access to the cells. J Exp Med. 1970 May 1;131(5):894–916. doi: 10.1084/jem.131.5.894. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nossal G. J., Lewis H., Warner N. L. Differential sensitivity of haemolytic plaque methods at various stages of the immune response. Cell Immunol. 1971 Feb;2(1):13–40. doi: 10.1016/0008-8749(71)90023-2. [DOI] [PubMed] [Google Scholar]
- Nossal G. J., Warner N. L., Lewis H. Incidence of cells simultaneously secreting IgM and IgG antibody to sheep erythrocytes. Cell Immunol. 1971 Feb;2(1):41–53. doi: 10.1016/0008-8749(71)90024-4. [DOI] [PubMed] [Google Scholar]
- Raff M. C. Two distinct populations of peripheral lymphocytes in mice distinguishable by immunofluorescence. Immunology. 1970 Oct;19(4):637–650. [PMC free article] [PubMed] [Google Scholar]
- Rosenstreich D. L., Blake J. T., Rosenthal A. S. The peritoneal exudate lymphocyte. I. Differences in antigen responsiveness between peritoneal exudate and lymph node lymphocytes from immunized guinea pigs. J Exp Med. 1971 Nov 1;134(5):1170–1186. doi: 10.1084/jem.134.5.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenthal A. S., Davie J. M., Rosenstreich D. L., Blake J. T. Depletion of antibody-forming cells and their precursors from complex lymphoid cell populations. J Immunol. 1972 Jan;108(1):279–281. [PubMed] [Google Scholar]
- Stobo J. D., Paul W. E. Functional heterogeneity of murine lymphoid cells. 3. Differential responsiveness of T cells to phytohemagglutinin and concanavalin A as a probe for T cell subsets. J Immunol. 1973 Feb;110(2):362–375. [PubMed] [Google Scholar]
- Stobo J. D., Rosenthal A. S., Paul W. E. Functional heterogeneity of murine lymphoid cells. I. Responsiveness to and surface binding of concanavalin A and phytohemagglutinin. J Immunol. 1972 Jan;108(1):1–17. [PubMed] [Google Scholar]
- Taub R. N., Lance E. M. Effects of lymphoid depletion on the distribution of 51Cr-labeled lymph node cells in mice. Transplantation. 1971 Jun;11(6):536–542. [PubMed] [Google Scholar]
- Tigelaar R. E., Asofsky R. Synergy among lymphoid cells mediating the graft-versus-host response. V. Derivation by migration in lethally irradiated recipients of two interacting subpopulations of thymus-derived cells from normal spleen. J Exp Med. 1973 Feb 1;137(2):239–253. doi: 10.1084/jem.137.2.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tigelaar R. E., Feldmann M. Synergy among thymocytes and peripheral lymph node cells in the in vitro generation of lymphocytes cytotoxic to alloantigens. Transplant Proc. 1973 Dec;5(4):1711–1715. [PubMed] [Google Scholar]
- Tubergen D. G., Feldman J. D., Pollock E. M., Lerner R. A. Production of macrophage migration inhibition factor by continuous cell lines. J Exp Med. 1972 Feb 1;135(2):255–266. doi: 10.1084/jem.135.2.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WARNER N. L., SZENBERG A., BURNET F. M. The immunological role of different lymphoid organs in the chicken. I. Dissociation of immunological responsiveness. Aust J Exp Biol Med Sci. 1962 Oct;40:373–387. doi: 10.1038/icb.1962.42. [DOI] [PubMed] [Google Scholar]
- Wagner H., Feldmann M. Cell-mediated immune response in vitro. I. A new in vitro system for the generation of cell-mediated cytotoxic activity. Cell Immunol. 1972 Mar;3(3):405–420. doi: 10.1016/0008-8749(72)90246-8. [DOI] [PubMed] [Google Scholar]
- Wagner H., Harris A. W., Feldmann M. Cell-mediated immune response in vitro. II. The role of thymus and thymus-derived lymphocytes. Cell Immunol. 1972 May;4(1):39–50. doi: 10.1016/0008-8749(72)90004-4. [DOI] [PubMed] [Google Scholar]
- Wagner H. Synergy during in vitro cytotoxic allograft responses. I. Evidence for cell interaction between thymocytes and peripheral T cells. J Exp Med. 1973 Dec 1;138(6):1379–1397. doi: 10.1084/jem.138.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshida T., Sonozaki H., Cohen S. The production of migration inhibition factor by B and T cells of the guinea pig. J Exp Med. 1973 Oct 1;138(4):784–797. doi: 10.1084/jem.138.4.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zatz M. M., Lance E. M. Lymphocyte trapping in tolerant mice. Nat New Biol. 1971 Dec 22;234(51):253–254. doi: 10.1038/newbio234253a0. [DOI] [PubMed] [Google Scholar]
- Zatz M. M., Lance E. M. The distribution of 51Cr-labeled lymphocytes into antigen-stimulated mice. Lymphocyte trapping. J Exp Med. 1971 Jul 1;134(1):224–241. doi: 10.1084/jem.134.1.224. [DOI] [PMC free article] [PubMed] [Google Scholar]