Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128

POTENTIATION OF THE T-LYMPHOCYTE RESPONSE TO MITOGENS

I. THE RESPONDING CELL

Igal Gery 1, Richard K Gershon 1, Byron H Waksman 1
PMCID: PMC2139184  PMID: 5033417

Abstract

Human and mouse lymphoid cells, stimulated by phytohemagglutinin (PHA) or lipopolysaccharide W (LPS), release supernatant factor(s) which are mitogenic for mouse thymocytes and which potentiate their responses to PHA or concanavalin A (Con A), The term LAF (lymphocyte-activating factor) is proposed for this activity. LAF not only enhances the mitotic responses of the less dense thymus subpopulations (A, B, and C) separable on discontinuous bovine serum albumin (BSA) gradients but also gives substantial responses in the otherwise inert cells of the denser fractions D and P. LAF does not exert a potentiating stimulatory effect on the responses of unfractionated mouse spleen cells, but does act synergistically with PHA on nonadherent spleen cells and on spleen cells of mice of several strains 5 days after irradiation and injection of thymocytes. Similarly LAF, which has no visible effect on unfractionated human peripheral blood cells, strongly potentiates the PHA response of column-purified lymphocytes, when these are cultured at low concentration. We conclude that LAF stimulates both central and peripheral T lymphocytes and enhances their responses to other stimulants.

Full Text

The Full Text of this article is available as a PDF (752.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaskov J. G., Halliday W. J. Requirement for lymphocyte-macrophage interaction in the response of mouse spleen cultures to pneumococcal polysaccharide. Cell Immunol. 1971 Aug;2(4):335–340. doi: 10.1016/0008-8749(71)90068-2. [DOI] [PubMed] [Google Scholar]
  2. Allison A. C., Davies A. J. Requirement of thymus-dependent lymphocytes for potentiation by adjuvants of antibody formation. Nature. 1971 Oct 1;233(5318):330–332. doi: 10.1038/233330a0. [DOI] [PubMed] [Google Scholar]
  3. Alter B. J., Bach F. H. Lymphocyte reactivity in vitro. I. Cellular reconstitution of purified lymphocyte response. Cell Immunol. 1970 Jul;1(2):207–218. doi: 10.1016/0008-8749(70)90008-0. [DOI] [PubMed] [Google Scholar]
  4. Andersson B., Blomgren H. Evidence for a small pool of immunocompetent cells in the mouse thymus. Its role in the humoral antibody response against sheep erythrocytes, bovine serum albumin, ovalbumin and the NIP determinant. Cell Immunol. 1970 Oct;1(4):362–371. doi: 10.1016/0008-8749(70)90014-6. [DOI] [PubMed] [Google Scholar]
  5. Bach F. H., Alter B. J., Solliday S., Zoschke D. C., Janis M. Lymphocyte reactivity in vitro. II. Soluble reconstituting factor permitting response of purified lymphocyte. Cell Immunol. 1970 Jul;1(2):219–227. doi: 10.1016/0008-8749(70)90009-2. [DOI] [PubMed] [Google Scholar]
  6. Blomgren H., Andersson B. Evidence for a small pool of immunocompetent cells in the mouse thymus. Exp Cell Res. 1969 Oct;57(2):185–192. doi: 10.1016/0014-4827(69)90140-2. [DOI] [PubMed] [Google Scholar]
  7. Colley D. G., Wu A. Y., Waksman B. H. Cellular differentiation in the thymus. 3. Surface properties of rat thymus and lymph node cells separated on density gradients. J Exp Med. 1970 Dec 1;132(6):1107–1121. doi: 10.1084/jem.132.6.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doenhoff M. J., Davies A. J., Leuchars E., Wallis V. The thymus and circulating lymphocytes of mice. Proc R Soc Lond B Biol Sci. 1970 Oct 13;176(1042):69–85. doi: 10.1098/rspb.1970.0035. [DOI] [PubMed] [Google Scholar]
  9. Dresser D. W., Taub R. N., Krantz A. R. The effect of localized injection of adjuvant material on the draining lymph node. II. Circulating lymphocytes. Immunology. 1970 May;18(5):663–670. [PMC free article] [PubMed] [Google Scholar]
  10. Dutton R. W., McCarthy M. M., Mishell R. I., Raidt D. J. Cell components in the immune response. IV. Relationships and possible interactions. Cell Immunol. 1970 Jul;1(2):196–206. doi: 10.1016/0008-8749(70)90007-9. [DOI] [PubMed] [Google Scholar]
  11. Epstein L. B., Cline M. J., Merigan T. C. The interaction of human macrophages and lymphocytes in the phytohemagglutinin-stimulated production of interferon. J Clin Invest. 1971 Apr;50(4):744–753. doi: 10.1172/JCI106545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fanger M. W., Hart D. A., Wells J. V., Nisonoff A. Enhancement by reducing agents of the transformation of human and rabbit peripheral lymphocytes. J Immunol. 1970 Oct;105(4):1043–1045. [PubMed] [Google Scholar]
  13. Gery I., Gershon R. K., Waksman B. H. Potentiation of cultured mouse thymocyte responses by factors released by peripheral leucocytes. J Immunol. 1971 Dec;107(6):1778–1780. [PubMed] [Google Scholar]
  14. Gery I., Krüger J., Spiesel S. Z. Stimulation of B-lymphocytes by endotoxin. Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T 6 T 6 thymus grafts. J Immunol. 1972 Apr;108(4):1088–1091. [PubMed] [Google Scholar]
  15. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gordon J., MacLean L. D. A lymphocyte-stimulating factor produced in vitro. Nature. 1965 Nov 20;208(5012):795–796. doi: 10.1038/208795a0. [DOI] [PubMed] [Google Scholar]
  17. Greaves M. F., Roitt I. M., Rose M. E. Effect of bursectomy and thymectomy on the responses of chicken peripheral blood lymphocytes to phytohaemagglutinin. Nature. 1968 Oct 19;220(5164):293–295. doi: 10.1038/220293a0. [DOI] [PubMed] [Google Scholar]
  18. Greaves M. F., Roitt I. M., Zamir R., Carnaghan R. B. Effect of anti-lymphocyte serum on responses of human peripheral-blood lymphocytes to specific and non-specific stimulants in vitro. Lancet. 1967 Dec 23;2(7530):1317–1319. doi: 10.1016/s0140-6736(67)90909-9. [DOI] [PubMed] [Google Scholar]
  19. Hanna M. G., Jr, Nettesheim P., Peters L. C. Evidence of functional microenvironments in lymphatic tissue response to antigen. Nat New Biol. 1971 Aug;232(33):204–206. doi: 10.1038/newbio232204a0. [DOI] [PubMed] [Google Scholar]
  20. Haskill J. S., Byrt P., Marbrook J. In vitro and in vivo studies of the immune response to sheep erythrocytes using partially purified cell preparations. J Exp Med. 1970 Jan 1;131(1):57–76. doi: 10.1084/jem.131.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hoffmann M., Dutton R. W. Immune response restoration with macrophage culture supernatants. Science. 1971 Jun 4;172(3987):1047–1048. doi: 10.1126/science.172.3987.1047. [DOI] [PubMed] [Google Scholar]
  22. Iversen J. G. Phytohemagglutinin response of recirculating and non-recirculating rat lymphocytes. Exp Cell Res. 1969 Aug;56(2):219–223. doi: 10.1016/0014-4827(69)90005-6. [DOI] [PubMed] [Google Scholar]
  23. Leckband E., Boyse E. A. Immunocompetent cells among mouse thymocytes: a minor population. Science. 1971 Jun 18;172(3989):1258–1260. doi: 10.1126/science.172.3989.1258. [DOI] [PubMed] [Google Scholar]
  24. Levis W. R., Robbins J. H. Effect of glass-adherent cells on the blastogenic response of 'purified' lymphocytes to phytohemagglutinin. Exp Cell Res. 1970 Jul;61(1):153–158. doi: 10.1016/0014-4827(70)90269-7. [DOI] [PubMed] [Google Scholar]
  25. Martial-Lasfargues C., Liacopoulos-Briot M., Halpern B. N. Culture des leucocytes sanguins de souris in vitro. Etude de l'action de la phytohémagglutinine (PHA) sur les lymphocytes de souris normales et thymectomisées. C R Seances Soc Biol Fil. 1966;160(11):2013–2019. [PubMed] [Google Scholar]
  26. Miller H. R., Avrameas S. Association between macrophages and specific antibody producing cells. Nat New Biol. 1971 Feb 10;229(6):184–185. doi: 10.1038/newbio229184a0. [DOI] [PubMed] [Google Scholar]
  27. Moore R. D., Schoenberg M. D. Synthesis of antibody by lymphocytes restimulated in vitro with antigen. J Reticuloendothel Soc. 1971 Mar;9(3):254–272. [PubMed] [Google Scholar]
  28. Möller G. Induction of DNA synthesis in human lymphocytes: interaction between non-specific mitogens and antigens. Immunology. 1970 Oct;19(4):583–598. [PMC free article] [PubMed] [Google Scholar]
  29. Oppenheim J. J., Leventhal B. G., Hersh E. M. The transformation of column-purified lymphocytes with nonspecific and specific antigenic stimuli. J Immunol. 1968 Aug;101(2):262–267. [PubMed] [Google Scholar]
  30. Parker C. W., Smith J. W., Steiner A. L. Early effects of phytohemagglutinin (PHA) on lymphocyte cyclic AMP levels. Int Arch Allergy Appl Immunol. 1971;41(1):40–46. doi: 10.1159/000230485. [DOI] [PubMed] [Google Scholar]
  31. RIEKE W. O., SCHWARZ M. R. THE CULTURE AND KARYOTYPE OF RAT LYMPHOCYTES STIMULATED WITH PHYTOHEMAGGLUTININ. Anat Rec. 1964 Dec;150:383–390. doi: 10.1002/ar.1091500406. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Schechter G. P. McFarland W,+MACFARLAND W: Interaction of lymphocytes and a radioresistant cell in PPD-stimulated human leukocyte cultures. J Immunol. 1970 Sep;105(3):661–669. [PubMed] [Google Scholar]
  34. Schwartz R. S., Ryder R. J., Gottlieb A. A. Macrophages and antibody synthesis. Prog Allergy. 1970;14:81–144. doi: 10.1159/000289374. [DOI] [PubMed] [Google Scholar]
  35. Schwarz M. R., Rieke W. O. The effect of phytohemagglutinin on rat thymus cells in vitro. Anat Rec. 1966 Aug;155(4):493–501. doi: 10.1002/ar.1091550402. [DOI] [PubMed] [Google Scholar]
  36. Shortman K., Diener E., Russell P., Armstrong W. D. The role of nonlymphoid accessory cells in the immune response to different antigens. J Exp Med. 1970 Mar 1;131(3):461–482. doi: 10.1084/jem.131.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shortman K., Palmer J. The requirement for macrophages in the in vitro immune response. Cell Immunol. 1971 Oct;2(5):399–410. doi: 10.1016/0008-8749(71)90051-7. [DOI] [PubMed] [Google Scholar]
  38. Spitznagel J. K., Allison A. C. Mode of action of adjuvants: effects on antibody responses to macrophage-associated bovine serum albumin. J Immunol. 1970 Jan;104(1):128–139. [PubMed] [Google Scholar]
  39. 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]
  40. THORBECKE G. J., BENACERRAF B. The reticulo-endothelial system and immunological phenomena. Prog Allergy. 1962;6:559–598. [PubMed] [Google Scholar]
  41. Takiguchi T., Adler W. H., Smith R. T. Cellular recognition in vitro by mouse lymphocytes. Effects of neonatal thymectomy and thymus graft restoration on alloantigen and PHA stimulation of whole and gradient-separated subpopulations of spleen cells. J Exp Med. 1971 Jan 1;133(1):63–80. doi: 10.1084/jem.133.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Takiguchi T., Adler W. H., Smith R. T. Identification of mouse thymus antigen recognition function in a minor, low-density, low-theta cell subpopulation. Cell Immunol. 1971 Aug;2(4):373–380. doi: 10.1016/0008-8749(71)90072-4. [DOI] [PubMed] [Google Scholar]
  43. Talmage D. W., Hemmingsen H. Cell interaction in antibody synthesis. J Allergy. 1969 Jun;43(6):323–335. doi: 10.1016/0021-8707(69)90077-x. [DOI] [PubMed] [Google Scholar]
  44. Tan T., Gordon J. Participation of three cell types in the anti-sheep red blood cell response in vitro. Separation of antigen-reactive cells from the precursors of antibody-forming cells. J Exp Med. 1971 Mar 1;133(3):520–533. doi: 10.1084/jem.133.3.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Taub R. N., Gershon R. K. The effect of localized injection of adjuvant material on the draining lymph node. 3. Thymus dependence. J Immunol. 1972 Feb;108(2):377–386. [PubMed] [Google Scholar]
  46. Unanue E. R., Askonas B. A., Allison A. C. A role of macrophages in the stimulation of immune responses by adjuvants. J Immunol. 1969 Jul;103(1):71–78. [PubMed] [Google Scholar]
  47. Weber W. T. Qualitative and quantitative studies on mixed homologous chicken thymus cell cultures. Clin Exp Immunol. 1970 Jun;6(6):919–940. [PMC free article] [PubMed] [Google Scholar]
  48. Weber W. T. The in vitro response of thymic lymphocytes of the pig to phytohemagglutinin. J Cell Physiol. 1966 Apr;67(2):285–299. doi: 10.1002/jcp.1040670209. [DOI] [PubMed] [Google Scholar]
  49. Whitfield J. F., MacManus J. P., Gillan D. J. The possible mediation by cyclic AMP of the stimulation of thymocyte proliferation by vasopressin and the inhibition of this mitogenic action by thyrocalcitonin. J Cell Physiol. 1970 Aug;76(1):65–76. doi: 10.1002/jcp.1040760110. [DOI] [PubMed] [Google Scholar]
  50. Whitfield J. F., MacManus J. P., Rixon R. H. The possible mediation by cyclic AMP of parathyroid hormone-induced stimulation of mitotic activity and deoxyribonucleic acid synthesis in rat thymic lymphocytes. J Cell Physiol. 1970 Apr;75(2):213–224. doi: 10.1002/jcp.1040750210. [DOI] [PubMed] [Google Scholar]
  51. Winkelstein A. Augmentation of PHA responsiveness in mixed thymus-marrow cultures. J Immunol. 1971 Jul;107(1):195–200. [PubMed] [Google Scholar]
  52. Wu A. Y., Waksman B. H. Cellular differentiation in the thymus. IV. Response of rat thymic subpopulations to anti-thymus serum and other nonspecific mitogens. Cell Immunol. 1972 Mar;3(3):516–528. doi: 10.1016/0008-8749(72)90256-0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES