Abstract
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.
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References
Thomas Y, Rogozinski L, Chess L: Relationship between human T cell functional heterogeneity and human T cell surface molecules. Immunol Rev 74:113–128, 1983
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, 1981
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, 1982
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, 1985
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, 1983
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, 1983
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, 1984
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, 1985
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, 1975
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, 1981
Abo T, Balch CM: A differentiation antigen on human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024, 1981
Breard JM, Reinherz EL, Kung PC, Goldstein G, Schlossman SF: A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol 124:1943–1948, 1980
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, 1983
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, 1981
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, 1983
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, 1984
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, 1981
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, 1982
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, 1977
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, 1979
Davis S, Rambotti P: Mitogen stimulation of chronic leukemic lymphcyotes: Defective phytohemagglutinin stimulation independent of immunologic cell surface markers. Blood 56:256–261, 1980
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, 1981
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, 1982
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, 1982
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, 1983
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Velardi, A., Clement, L.T. & Grossi, C.E. 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. J Clin Immunol 5, 329–339 (1985). https://doi.org/10.1007/BF00918252
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DOI: https://doi.org/10.1007/BF00918252