Abstract
Using limiting dilutions of responding cells in mouse mixed leukocyte cultures, we obtained direct estimates of the minimum frequency of precursors of cytotoxic T lymphocytes (CTL.P) for a variety of antigens. Depending on the strain combination, there were as many as 4- 15 CTL.P reactive to DBA/2 among 10(4) lymph node cells. Taking into account that only 5-10% of peripheral T lymphocytes have the potential to develop into cytotoxic T lymphocytes (CTLs) (6), this implies that at least 1-2% of all CTL.P are responsive to any given H-2 haplotype difference. Precursors of cytotoxic cells thus have the same high frequency of cells reactive to alloantigens of the major histocompatibility complex as found among proliferating cells in graft- vs.-host reactions and mixed lymphocyte interactions. The frequencies of CTL.P reactive to xenoantigens (rat) or trinitrophenyl-modified self were less than half the frequency of alloreactive CTL.P. A minority of the CTL.P specific for one H-2 haplotype were also reactive to a third party H-2 haplotype, presumably on the basis of recognition of shared determinants. By dilution of sensitized cells from single microcultures, it was shown that a single CTL.P undergoes a minimum of three to four cell divisions and generates at least 8-16 CTLs after antigenic activation.
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- Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes. J Exp Med. 1974 Jul 1;140(1):19–37. doi: 10.1084/jem.140.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Atkins R. C., Ford W. L. Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes. J Exp Med. 1975 Mar 1;141(3):664–680. doi: 10.1084/jem.141.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bach F. H., Bock H., Graupner K., Day E., Klostermann H. Cell kinetic studies in mixed leukocyte cultures: an in vitro model of homograft reactivity. Proc Natl Acad Sci U S A. 1969 Feb;62(2):377–384. doi: 10.1073/pnas.62.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bach F. H., Segall M., Zier K. S., Sondel P. M., Alter B. J., Bach M. L. Cell mediated immunity: separation of cells involved in recognitive and destructive phases. Science. 1973 Apr 27;180(4084):403–406. doi: 10.1126/science.180.4084.403. [DOI] [PubMed] [Google Scholar]
- Bach M. L., Alter B. J., Lightbody J. J., Bach F. H. Abrogation of cytotoxicity of mixed leukocyte cultures. Transplant Proc. 1972 Jun;4(2):169–172. [PubMed] [Google Scholar]
- Bevan M. J., Langman R. E., Cohn M. H-2 antigen-specific cytotoxic T cells induced by concanavalin A: estimation of their relative frequency. Eur J Immunol. 1976 Mar;6(3):150–156. doi: 10.1002/eji.1830060303. [DOI] [PubMed] [Google Scholar]
- Beverley P. C., Woody J., Dunkley M., Feldmann M., McKenzie I. Separation of suppressor and killer T cells by surgace phenotype. Nature. 1976 Aug 5;262(5568):495–497. doi: 10.1038/262495a0. [DOI] [PubMed] [Google Scholar]
- Brondz B. D., Snegiröva A. E. Interaction of immune lymphocytes with the mixtures of target cells possessing selected specificities of the H-2 immunizing allele. Immunology. 1971 Apr;20(4):457–468. [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Jandinski J. The relationship of cell division to the generation of cytotoxic activity in mixed lymphocyte culture. J Exp Med. 1974 Dec 1;140(6):1712–1716. doi: 10.1084/jem.140.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantor H., Shen F. W., Boyse E. A. Separation of helper T cells from suppressor T cells expressing different Ly components. II. Activation by antigen: after immunization, antigen-specific suppressor and helper activities are mediated by distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1391–1340. doi: 10.1084/jem.143.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
- Ford W. L., Simmonds S. J., Atkins R. C. Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex. J Exp Med. 1975 Mar 1;141(3):681–696. doi: 10.1084/jem.141.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter P., Kettman J. R. Mode of action of a supernatant activity from T-cell cultures that nonspecifically stimulates the humoral immune response. Proc Natl Acad Sci U S A. 1974 Feb;71(2):512–516. doi: 10.1073/pnas.71.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jandinski J., Cantor H., Tadakuma T., Peavy D. L., Pierce C. W. Separation of helper T cells from suppressor T cells expressing different Ly components. I. Polyclonal activation: suppressor and helper activities are inherent properties of distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1382–1390. doi: 10.1084/jem.143.6.1382. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindahl F., Peck A. B., Bach F. H. Specificity of cell-mediated lympholysis for public and private H-2 determinants. Scand J Immunol. 1975 Sep;4(5-6):541–553. doi: 10.1111/j.1365-3083.1975.tb02660.x. [DOI] [PubMed] [Google Scholar]
- Lindahl K. F., Wilson D. B. Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro. J Exp Med. 1977 Mar 1;145(3):500–507. doi: 10.1084/jem.145.3.500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nabholz M., Vives J., Young H. M., Meo T., Miggiano V., Rijnbeek A., Shreffler D. C. Cell-mediated cell lysis in vitro: genetic control of killer cell production and target specificities in the mouse. Eur J Immunol. 1974 May;4(5):378–387. doi: 10.1002/eji.1830040514. [DOI] [PubMed] [Google Scholar]
- Nedrud J., Touton M., Clark W. R. The requirement for DNA synthesis and gene expression in the generation of cytotoxicity in vitro. J Exp Med. 1975 Oct 1;142(4):960–973. doi: 10.1084/jem.142.4.960. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peavy D. L., Pierce C. W. Cell-mediated immune responses in vitro. II. Simultaneous generation of cytotoxic lymphocyte responses to two sets of alloantigens of limited cross-reactivity. J Immunol. 1975 Dec;115(6):1515–1520. [PubMed] [Google Scholar]
- Peavy D. L., Pierce C. W. Cell-mediated immune responses in vitro. III. Elimination of specific cytotoxic lymphocyte responses by 3H-thymidine suicide. J Immunol. 1975 Dec;115(6):1521–1524. [PubMed] [Google Scholar]
- Quintáns J., Lefkovits I. Precursor cells specific to sheep red cells in nude mice. Estimation of frequency in the microculture system. Eur J Immunol. 1973 Jul;3(7):392–397. doi: 10.1002/eji.1830030704. [DOI] [PubMed] [Google Scholar]
- Schilling R. M., Phillips R. A., Miller R. G. Requirement for non-T cells in the generation of cytotoxic T lymphocytes in vitro. I. Use of nude mice as source of non-T cells. J Exp Med. 1976 Jul 1;144(1):241–258. doi: 10.1084/jem.144.1.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
- Skinner M. A., Marbrook J. An estimation of the frequency of precursor cells which generate cytotoxic lymphocytes. J Exp Med. 1976 Jun 1;143(6):1562–1567. doi: 10.1084/jem.143.6.1562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sondel P. M., Bach F. H. Recognitive specificity of human cytotoxic T lymphocytes. I. Antigen-specific inhibition of human cell-mediated lympholysis. J Exp Med. 1975 Dec 1;142(6):1339–1348. doi: 10.1084/jem.142.6.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wagner H., Feldmann M., Boyle W., Schrader J. W. Cell-mediated immune response in vitro. 3. The requirement for macrophages in cytotoxic reactions against cell-bound and subcellular alloantigens. J Exp Med. 1972 Aug 1;136(2):331–343. doi: 10.1084/jem.136.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wagner H., Röllinghoff M., Nossal G. J. T-cell-mediated immune responses induced in vitro: a probe for allograft and tumor immunity. Transplant Rev. 1973;17(0):3–36. doi: 10.1111/j.1600-065x.1973.tb00122.x. [DOI] [PubMed] [Google Scholar]
- Wilson D. B., Blyth JL NOWELL P. C. Quantitative studies on the mixed lymphocyte interaction in rats. 3. Kinetics of the response. J Exp Med. 1968 Nov 1;128(5):1157–1181. doi: 10.1084/jem.128.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]