Age-related changes of the multidrug resistance P-glycoprotein function in normal human peripheral blood T lymphocytes.

The multidrug resistance P-glycoprotein is a transmembrane efflux pump expressed by lymphocytes and is involved in their cytolytic activity. In the present study, we investigated the age-related changes of P-glycoprotein function in normal peripheral blood lymphocytes. Blood samples from 90 normal volunteers (age range, 0 to 86 years) were analyzed. P-glycoprotein function was assessed by the flow cytometric rhodamine 123 assay. P-glycoprotein function was highest in cord blood and progressively declined with age in peripheral blood T CD4+ and CD8+ cells. In contrast, P-glycoprotein function did not vary with age in CD19+ B or CD16+CD56+ natural killer cells. These data suggest that the decline in P-glycoprotein function in T CD4+ and CD8+ lymphocytes as a function of age may contribute to the decrease in T cell cytolytic activity with aging.

[1]  M. Fromm,et al.  The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. , 2001, Pharmacogenetics.

[2]  T. Tsuruo,et al.  Altered Expression and Function of P-Glycoprotein (170 Kda), Encoded by the MDR 1 Gene, in T Cell Subsets from Aging Humans , 1997, Journal of Clinical Immunology.

[3]  Charles W. Taylor,et al.  Inhibition of cell-mediated cytolysis and P-glycoprotein function in natural killer cells by verapamil isomers and cyclosporine a analogs , 1995, Journal of Clinical Immunology.

[4]  I. Roninson,et al.  Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells , 1991, Cell.

[5]  M. Zago,et al.  Influence of functional MDR 1 gene polymorphisms on P-glycoprotein activity in CD 34 + hematopoietic stem cells , 2022 .

[6]  R. Calado,et al.  Reduced function of the multidrug resistance P‐glycoprotein in CD34+ cells of patients with aplastic anaemia , 2002, British journal of haematology.

[7]  C. Cass,et al.  Multidrug transporter p‐glycoprotein 170 as a differentiation antigen on normal human lymphocytes and thymocytes: Modulation with differentiation stage and during aging , 1995, American journal of hematology.

[8]  K. Linton,et al.  Structure of the multidrug resistance P-glycoprotein. , 1997, Seminars in cancer biology.

[9]  J. Rossi,et al.  Multicentric evaluation of the MDR phenotype in leukemia , 1997, Leukemia.

[10]  I. Roninson,et al.  Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. , 1992, Blood.

[11]  Sudhir Gupta.  Membrane Signal Transduction in T Cells in Aging Humans a , 1989, Annals of the New York Academy of Sciences.

[12]  T. Tsuruo,et al.  Preferential expression and activity of multidrug resistance gene 1 product (P-glycoprotein), a functionally active efflux pump, in human CD8 + T cells: A role in cytotoxic effector function , 1992, Journal of Clinical Immunology.

[13]  R. Calado,et al.  Decreased activity of the multidrug resistance P‐glycoprotein in acquired aplastic anaemia: possible pathophysiologic implications , 1998, British journal of haematology.

[14]  R. Calado,et al.  Age-related changes of P-glycoprotein-mediated rhodamine 123 efflux in normal human bone marrow hematopoietic stem cells , 2003, Leukemia.

[15]  Richard A. Miller.  The Aging Immune System: Primer and Prospectus , 1996, Science.

[16]  I. Roninson,et al.  Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. , 1992, Blood.

[17]  S. Zhao,et al.  Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes. , 1996, Blood.

[18]  G. Raghu,et al.  Monoclonal antibodies against P-glycoprotein, an MDR1 gene product, inhibit interleukin-2 release from PHA-activated lymphocytes. , 1996, Experimental hematology.

[19]  A. Schinkel,et al.  The physiological function of drug-transporting P-glycoproteins. , 1997, Seminars in cancer biology.

[20]  S. Zhao,et al.  Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype. , 1992, Blood.

[21]  Sudhir Gupta,et al.  P-glycoprotein (MDR 1 gene product) in cells of the immune system: Its possible physiologic role and alteration in aging and human immunodeficiency virus-1 (HIV-1) infection , 1993, Journal of Clinical Immunology.

[22]  A. B. Kay,et al.  Lymphocytes , 1991 .

[23]  N. Holbrook,et al.  Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. , 1988, The Journal of clinical investigation.

[24]  G. Gastl,et al.  Differential activity of P‐glycoprotein in normal blood lymphocyte subsets , 1998, British journal of haematology.

[25]  M. Zago,et al.  Influence of functional MDR1 gene polymorphisms on P-glycoprotein activity in CD34+ hematopoietic stem cells. , 2002, Haematologica.

[26]  Sudhir Gupta,et al.  Natural killing and antibody-dependent cytotoxicity by lymphocyte subpopulations in young and aging humans , 1981, Journal of Clinical Immunology.

[27]  C. F. Lange.  Immunology of Aging , 2019, Frontiers Research Topics.