Mitogenic and Non-Mitogenic Induction of Lymphocytic Invasion: Dual Parameter flow Cytometric Analysis

  • S. Ratner
  • D. Lichlyter
Part of the Developments in Oncology book series (DION, volume 77)


It has been well established that mitogenic activation produces profound alterations in the migratory behavior of lymphocytes. Activated, blastic T and B cells down-regulate homing receptors which mediate adhesion to the high endothelium of peripheral lymph nodes (1–3). Concurrently, they up-regulate adhesion receptors for extracellular matrix components and for ligands typical of inflammatory endothelium (4–6). The result is a change in traffic patterns, from extravasation into lymph nodes to extravasation into nonlymphoid tissue, especially inflamed tissue (7,8). After the immune response terminates, memory cells, the long-lived residual progeny of the blasts, remain. Memory helper T cells, even when not proliferating, retain the non-homing, inflammation-seeking behavior of the parental blasts (9–11). There are indications that other memory lymphocyte subsets follow similar trends (12,13).


Acridine Orange Peripheral Lymph Node Cell Cycle Profile Homing Receptor Lymph Node Homing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hamann A, Jablonski-Westrich D, Scholz K-U, et al: Regulation of lymphocyte homing, I. Alterations in homing receptor expression and organ-specific high endothelial venule binding of lymphocytes upon activation. J. Immunol. 140:737–743, 1988.PubMedGoogle Scholar
  2. 2.
    Jung TM, Gallatin WM, Weissman IL, Dailey MO: Down-regulation of homing receptors after T cell activation. J. Immunol. 141:4110–4117, 1988.PubMedGoogle Scholar
  3. 3.
    Steen PD, McGregor JR, Lehman CM, Samlowski WE: Changes in homing receptor expression on murine lymphokine-activated killer cells during IL-2 exposure. J. Immunol. 143:4324–4330, 1989.PubMedGoogle Scholar
  4. 4.
    Dustin ML, Springer TA: Role of lymphocyte adhesion receptors in transient interactions and cell locomotion. Ann. Rev. Immunol. 9:27–66 1991.CrossRefGoogle Scholar
  5. 5.
    Pober JS, Cotran RS: Immunologic interactions of T lymphocytes with vascular endothelium. Adv. Immunol. 50:261–302, 1991.PubMedCrossRefGoogle Scholar
  6. 6.
    Shimizu Y, Shaw S: Lymphocyte interactions with extracellular matrix. FASEB J. 5:2292–2299, 1991.PubMedGoogle Scholar
  7. 7.
    Parrott DMV, Wilkinson PC: Lymphocyte locomotion and migration. Progr. Allergy 28:193–284, 1981.Google Scholar
  8. 8.
    Hamann A: Mechanisms of lymphocyte traffic and cell targeting. Int. J. Cancer Suppl. 7:19–23, 1992.PubMedGoogle Scholar
  9. 9.
    Pitzalis C, Kingsley GH, Covelli M, et al: Selective migration of the human helper-inducer memory subset: Confirmation by in vivo cellular kinetic studies. Eur. J. Immunol. 21:369–376, 1991.PubMedCrossRefGoogle Scholar
  10. 10.
    Cush JJ, Pietschmann P, Oppenheimer-Marks N, Lipsky PE: The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium. Arthritis Rheum. 35:1434–1444, 1992.PubMedCrossRefGoogle Scholar
  11. 11.
    Mackay CR: Migration pathways and immunologic memory among T lymphocytes. Semin. Immunol. 4:51–58, 1992.PubMedGoogle Scholar
  12. 12.
    Akbar AN, Amlot PL, Timms A, et al: The development of primed/memory CD8+ lymphocytes in vitro and in rejecting kidneys after transplantation. Clin. Exp. Immunol. 81:225–231, 1990.PubMedCrossRefGoogle Scholar
  13. 13.
    Mobley JL, Dailey MO: Regulation of adhesion molecule expression by CD8 T cells in vivo. I. Differential regulation of gp90EMEL-14 (LECAM-1), Pgp-1, LFA-1, and VLA-4a during the differentiation of cytotoxic T lymphocytes induced by allografts. J. Immunol. 148:2348–2356, 1992.PubMedGoogle Scholar
  14. 14.
    Pilaro AM, Sayers TJ, McCormick KL, et al: An improved in vitro assay to quantitate Chemotaxis of rat peripheral large granular blood lymphocytes. J. Immunol. Methods 135:213–224, 1990.PubMedCrossRefGoogle Scholar
  15. 15.
    Arencibia I, Sundqvist K-G: Collagen receptor in T lymphocytes and the control of lymphocyte motility. Eur. J. Immunol. 19:929–934, 1989.PubMedCrossRefGoogle Scholar
  16. 16.
    Davis JM, St John J, Cheung HT: Haptotactic activity of fibronectin on lymphocyte migration in vitro. Cell. Immunol. 129:67–69, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Somersalo K, Saksela E: Fibronectin facilitates the migration of human natural killer cells. Eur. J. Immunol. 21:35–42, 1991.PubMedCrossRefGoogle Scholar
  18. 18.
    Wilkinson PC: Leukocyte locomotion and accumulation: The contributions of cell polarity and cell growth. In: Leukocyte Emigration and its Sequelae. Satellite Symposium of the Sixth International Congress of Immunology, Z Movat (ed), Karger, Basel, pp. 1–13, 1986.Google Scholar
  19. 19.
    Klein V, Kantwerk-Funke G, Zanker KS: Two-dimensional and three-dimensional behavior of native or stimulated peripheral blood lymphocytes. Proc. AACR 31:299, 1990.Google Scholar
  20. 20.
    Applegate KG, Blach CM, Peius NR: In vitro migration of lymphocytes through collagen matrix: Arrested locomotion in tumor-infiltrating lymphocytes. Cancer Res. 50:7153–7158, 1990.PubMedGoogle Scholar
  21. 21.
    Ratner S, Patrick P, Bora G: Lymphocyte development of motility in extracellular matrix during IL-2 stimulation. J. Immunol. 149:681–688, 1992.PubMedGoogle Scholar
  22. 22.
    Ratner S: Lymphocyte migration through extracellular matrix. Invasion Metastasis 12:82–100, 1992.PubMedGoogle Scholar
  23. 23.
    Laskin DL, Gardner CR, Laskin JD: Induction of Chemotaxis in mouse peritoneal macrophages by activation of protein kinase C. J. Leukocyte Biol. 41:474–480, 1987.PubMedGoogle Scholar
  24. 24.
    Prpic V, Uhing RJ, Weiel JE, et al: Biochemical and functional responses stimulated by platelet-activating factor in murine peritoneal macrophages. J. Cell Biol. 107:363–372, 1988.PubMedCrossRefGoogle Scholar
  25. 25.
    Blood CH, Zetter BR: Membrane-bound protein kinase C modulates receptor affinity and chemotactic responsiveness of Lewis lung carcinoma sublines to an elastin-derived peptide. J. Biol. Chem. 264:10614–10620, 1989.PubMedGoogle Scholar
  26. 26.
    Schwartz GK, Redwood SM, Ohnuma T, et al: Inhibition of invasion of invasive human bladder carcinoma cells by protein kinase C inhibitor staurosporine. J. Natl. Cancer Inst. 82:1753–1756, 1990.PubMedCrossRefGoogle Scholar
  27. 27.
    Wilkinson PC, Lackie JM, Haston WS, Islam LN: Effects of phorbol esters on shape and locomotion of human blood lymphocytes. J. Cell Science 90:645–655, 1988.PubMedGoogle Scholar
  28. 28.
    Keller HU, Niggli V, Zimmerman A: Diacylglycerols and PMA induce actin polymerization and distinct shape changes in lymphocytes. Relationship to fluid pinocytosis and locomotion. J. Cell Science 93:457–465, 1989.PubMedGoogle Scholar
  29. 29.
    Oppenheimer-Marks N, Davis LS, Lipsky PE: Human T lymphocyte adhesion to endothelial cells and transendothelial migration. Alteration of receptor use relates to activation status of both the T cell and the endothelial cell. J. Immunol. 145:140–148, 1990.PubMedGoogle Scholar
  30. 30.
    Darzynkiewicz Z: Differential staining of DNA and RNA in intact cells and isolated cell nuclei with acridine orange. Methods in Cell Biology 33:285–298, 1990.PubMedCrossRefGoogle Scholar
  31. 31.
    Gilbert KM, Ernst DN, Hobbs MV, Weigle WO: Effects of tolerance induction on early cell cycle programsion by TH1… blood lymphocytes. Immunol. 71:417–422, 1990.Google Scholar
  32. 34.
    Ratner S: Interleukin-2-stimulated lymphocytes. Relationship between motility into protein matrix and in vivo localization in normal and neoplastic tissue. J. Natl. Cancer Inst. 82:612–615, 1990.PubMedCrossRefGoogle Scholar
  33. 35.
    Grzesiak JJ, Davis GE, Kirchhofer D, Pierschbacher MD: Regulation of alpha-2 beta-I-mediated fibroblast migration on Type I collagen by shifts in the concentrations of extracellular Mg2+ and Ca2+. J. Cell Biol. 117:1109–1117, 1992.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • S. Ratner
  • D. Lichlyter

There are no affiliations available

Personalised recommendations