Abstract
Density distribution analysis in continuous gradients of albumin has been used to study the development of cytotoxic lymphocytes (CL), to separate and characterize the progenitors of CL, and to determine their relationship to subpopulations of T cells. CL progenitors in the thymus were a homogeneous, medium-density population, distinct from the typical, dense, thymus small-lymphocyte. Activity seemed to be associated with one minor subpopulation of cells with surface antigenic properties characteristic of peripheral T cells (high levels of H-2 antigen, low levels of θ-antigen). CL progenitors in the spleen differed from those in the thymus and normally had the high buoyant density of typical small T lymphocytes. In states of antigenic stimulation, some lighter-density CL progenitors were found in the spleen. The buoyant density of the CL population developing in the spleens of immunized animals showed progressive changes with time. Early, "immature" CL had the light-density characteristics of large, activated lymphocytes. As the response developed, the density of the CL population increased, and finally approached that of CL progenitors and of typical small lymphocytes. The data suggest that density subpopulations of T cells represent stages in the development of immunocompetent cells. Possible differentiation pathways of T lymphocytes in the thymus and in the spleen are discussed.
Full Text
The Full Text of this article is available as a PDF (853.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brunner K. T., Mauel J., Cerottini J. C., Chapuis B. Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology. 1968 Feb;14(2):181–196. [PMC free article] [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]
- Cerottini J. C., Brunner K. T. Localization of mouse isoantigens on the cell surface as revealed by immunofluorescence. Immunology. 1967 Oct;13(4):395–403. [PMC free article] [PubMed] [Google Scholar]
- Cerottini J. C., Nordin A. A., Brunner K. T. Cellular and humoral response to transplantation antigens. I. Development of alloantibody-forming cells and cytotoxic lymphocytes in the graft-versus-host reaction. J Exp Med. 1971 Aug 1;134(2):553–564. doi: 10.1084/jem.134.2.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerottini J. C., Nordin A. A., Brunner K. T. Specific in vitro cytotoxicity of thymus-derived lymphocytes sensitized to alloantigens. Nature. 1970 Dec 26;228(5278):1308–1309. doi: 10.1038/2281308a0. [DOI] [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]
- Haskill J. S. Density distribution analysis of antigen sensitive cells in the rat. Nature. 1967 Dec 23;216(5121):1229–1231. doi: 10.1038/2161229a0. [DOI] [PubMed] [Google Scholar]
- Haskill J. S. Density distribution analysis of antigen-sensitive cells in the rat. J Exp Med. 1969 Oct 1;130(4):877–893. doi: 10.1084/jem.130.4.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kraft N., Shortman K. Differentiation of antibody-forming cells in toad spleen. A study using density and sedimentation velocity cell separation. J Cell Biol. 1972 Feb;52(2):438–452. doi: 10.1083/jcb.52.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller J. F., Brunner K. T., Sprent J., Russell P. J., Mitchell G. F. Thymus-derived cells as killer cells in cell-mediated immunity. Transplant Proc. 1971 Mar;3(1):915–917. [PubMed] [Google Scholar]
- Miller J. F., Osoba D. Current concepts of the immunological function of the thymus. Physiol Rev. 1967 Jul;47(3):437–520. doi: 10.1152/physrev.1967.47.3.437. [DOI] [PubMed] [Google Scholar]
- Raidt D. J., Mishell R. I., Dutton R. W. Cellular events in the immune response : analysis and in vitro response of mouse spleen cell populations separated by differential flotation in albumin gradients. J Exp Med. 1968 Oct 1;128(4):681–698. doi: 10.1084/jem.128.4.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shortman K. The density distribution of thymus, thoracic duct and spleen lymphocytes. J Cell Physiol. 1971 Jun;77(3):319–330. doi: 10.1002/jcp.1040770306. [DOI] [PubMed] [Google Scholar]
- Shortman K. The separation of different cell classes from lymphoid organs. II. The purification and analysis of lymphocyte populations by equilibrium density gradient centrifugation. Aust J Exp Biol Med Sci. 1968 Aug;46(4):375–396. doi: 10.1038/icb.1968.32. [DOI] [PubMed] [Google Scholar]
- Staples P. J., Gery I., Waksman B. H. Role of the thymus in tolerance. 3. Tolerance to bovine gamma globulin after direct injection of antigen into the shielded thymus of irradiated rats. J Exp Med. 1966 Aug 1;124(2):127–139. doi: 10.1084/jem.124.2.127. [DOI] [PMC free article] [PubMed] [Google Scholar]