Journal of Clinical Immunology

, Volume 5, Issue 5, pp 329–339 | Cite as

Quantitative and functional analysis of a human lymphocyte subset with the T-helper (Leu 3/T 4+) phenotype and natural killer (NK)-cell characteristics in patients with malignancy

  • Andrea Velardi
  • Loran T. Clement
  • Carlo E. Grossi
Original Articles


Approximately 20% of normal blood lymphocytes expressing the T-helper (Leu 3/T 4+) surface phenotype display natural killer (NK)-like features such as cytoplasmic granules and the ability to bind NK-cell targets. In this study, we have assessed the frequency, phenotypic features, and functional capabilities of such cells in a variety of lymphoid malignancies or solid tumors. In each patient group, the percentage of granular lymphocytes within the Leu 3/T 4+ T-helper subset was significantly increased. A large percentage of these cells coexpressed the Leu 7 or Leu 15 marker. When Leu 3+ cells from patients with high proportions of such NK-like cells (or Leu 3+-Leu 15+ cells from selected patients) were isolated with a fluorescence-activated cell sorter, these cells did not proliferate in response to allogeneic cells or T-cell mitogens, nor did they provide help for B-cell differentiation. They also did not suppress T-cell proliferative responses or B-cell differentiation. Freshly prepared Leu 3+ granular lymphocytes did not display NK-cell cytotoxic functions. However, after short-term culture in the presence of phytohemagglutinin (PHA), Leu 3+-Leu 15+ cells expressed T-cell growth factor (TCGF) receptors, had a detectable proliferative response to exogenous TCGF, and acquired the ability to lyse NK-cell targets. These studies demonstrate that, in a variety of malignancies, the lymphocyte subpopulation expressing the T-helper (Leu 3/T 4+) phenotype may be comprised largely of cells with NK-like features and functional capabilities distinct from those of classical helper T cells.

Key words

Natural killer (NK) cells lymphocyte subpopulations cytotoxicity malignancy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Thomas Y, Rogozinski L, Chess L: Relationship between human T cell functional heterogeneity and human T cell surface molecules. Immunol Rev 74:113–128, 1983Google Scholar
  2. 2.
    Zicca A, Leprini A, Cadoni A, Franzi AT, Ferrarini M, Grossi CE: Ultrastructural localization of alpha-naphthyl acid esterase in human TM lymphocytes. Am J Pathol 105:40–46, 1981Google Scholar
  3. 3.
    Armitage RJ, Linch DC, Worman CP, Cawley JC: The morphology and cytochemistry of human T-cell subpopulations defined by monoclonal antibodies and Fc receptors. Br J Haematol 52:605–613, 1982Google Scholar
  4. 4.
    Velardi A, Grossi CE, Cooper MD: A large subpopulation of lymphocytes with T helper phenotype Leu 3/T 4+) exhibits the property of binding to NK cell targets and granular lymphocyte morphology. J Immunol 134:58–64, 1985Google Scholar
  5. 5.
    Poppema S, Visser L, DeLeij L: Reactivity of presumed natural killer cell antibody Leu 7 with intrafollicular T lymphocytes. Clin Exp Immunol 54:834–837, 1983Google Scholar
  6. 6.
    Porwit-Ksiazek A, Ksiazek T, Biberfeld P: Leu 7+ (HNK-1+) cells. I. Selective compartmentalization of Leu 7+ cells with different immunophenotypes in lymphatic tissues and blood. Scand J Immunol 18:485–493, 1983Google Scholar
  7. 7.
    Pizzolo G, Semenzato G, Chilosi M, Morittu L, Ambrosetti A, Warner N, Bofill M, Janossy G: Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions. Clin Exp Immunol 57:195–206, 1984Google Scholar
  8. 8.
    Velardi A, Prchal JT, Prasthofer EF, Grossi CE: Expression of NK-lineage markers on peripheral blood lymphocytes with T-helper (Leu 3+/T 4+) phenotype in B-cell chronic lymphocytic leukemia. Blood 65:149–155, 1985Google Scholar
  9. 9.
    Pellegrino MA, Ferrone S, Dierich MP, Reisfield RA: Enhancement of sheep red blood cell-human lymphocyte rosette formation by the sulfhydryl compound 2-aminoethylisothiouronium bromide. Clin Immunol Immunopathol 23:324–333, 1975Google Scholar
  10. 10.
    Ledbetter JA, Evans RL, Lipinski M, Cunningham-Rundle C, Good RA, Herzenberg LA: Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and T cytotoxic suppressor subpopulations in mouse and man. J Exp Med 153:310–323, 1981Google Scholar
  11. 11.
    Abo T, Balch CM: A differentiation antigen on human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024, 1981Google Scholar
  12. 12.
    Breard JM, Reinherz EL, Kung PC, Goldstein G, Schlossman SF: A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol 124:1943–1948, 1980Google Scholar
  13. 13.
    Landay A, Gartland GL, Clement LT: Characterization of a phenotypically distinct subpopulation of Leu2+ cells which suppresses T-cell proliferative response. J Immunol 131:2757–2761, 1983Google Scholar
  14. 14.
    Uchiyama T, Broder S, Waldmann TA: A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of an anti-Tac antibody and distribution of Tac (+) cells. J Immunol 126:1393–1397, 1981Google Scholar
  15. 15.
    Clement LT, Dagg MK, Lehmeyer JE, Kiyotaki M: Two phenotypically distinct suppressor T cell subpopulations inhibit the induction of B cell differentiation by phytohemagglutinin. J Immunol 131:1214–1217, 1983Google Scholar
  16. 16.
    Clement LT, Grossi CE, Gartland GL: Morphologic and phenotypic features of the subpopulation of Leu 2+ cells that suppresses B cell differentiation. J Immunol 133:2461–2468, 1984Google Scholar
  17. 17.
    Thomas Y, Rogozinski L, Irigoyen O, Friedman SM, Kung PC, Goldstein G, Chess L: Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT 4+ population. J Exp Med 154:459–467, 1981Google Scholar
  18. 18.
    Thomas Y, Rogozinski L, Irigoyen O, Shen H, Talle MA, Goldstein G, Chess L: Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT 4+ population belong to a distinct subset. J Immunol 128:1386–1390, 1982Google Scholar
  19. 19.
    Smith JB, Knowlton RP, Koons S: Immunologic studies in chronic lymphocytic leukemia: Defective stimulation of T-cell proliferation in autologous mixed lymphocyte culture. J Natl Cancer Inst 58:579–585, 1977Google Scholar
  20. 20.
    Chiorazzi N, Fu SM, Montazeri G, Kunkel HG, Rai K, Gee R: T cell helper defect in patients with chronic lymphocytic leukemia. J Immunol 122:1087–1090, 1979Google Scholar
  21. 21.
    Davis S, Rambotti P: Mitogen stimulation of chronic leukemic lymphcyotes: Defective phytohemagglutinin stimulation independent of immunologic cell surface markers. Blood 56:256–261, 1980Google Scholar
  22. 22.
    Han T, Ozer H, Henderson ES, Dadey B, Nussbaum-Blumenson A, Barcos M: Defective immunoregulatory T-cell function in chronic lymphocytic leukemia. Blood 58:1182–1189, 1981Google Scholar
  23. 23.
    Han T, Bloom ML, Dadey D, Bennett G, Minowada J, Sandberg AA, Ozer H: Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: Evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype or clinical status. Blood 60:1075–1081, 1982Google Scholar
  24. 24.
    Platsoucas CD, Galinski M, Kempin S, Reich L, Clarkson B, Good RA: Abnormal T lymphocyte subpopulations in patients with B cell chronic lymphocytic leukemia: An analysis by monoclonal antibodies. J Immunol 123:2305–2312, 1982Google Scholar
  25. 25.
    Lauria F, Foa R, Mantovani V, Fierro MT, Catovsky D, Tura S: T-cell functional abnormality in B-chronic lymphocytic leukemia: Evidence for a defect of the T-helper subset. Brit J Haematol 54:277–283, 1983Google Scholar

Copyright information

© Plenum Publishing Corporation 1985

Authors and Affiliations

  • Andrea Velardi
    • 1
  • Loran T. Clement
    • 1
  • Carlo E. Grossi
    • 1
    • 2
  1. 1.Cellular Immunobiology Unit of the Tumor InstituteThe University of Alabama at BirminghamBirmingham
  2. 2.Department of PathologyThe University of Alabama at BirminghamBirmingham

Personalised recommendations