Differential activity of P-glycoprotein in normal blood lymphocyte subsets

To better understand the phenomenon of P-glycoprotein (P-170) expression we investigated lymphocyte subpopulations for P-170 function in healthy volunteers. Studies were based on three-colour flow cytometry including the fluorescent probe rhodamine 123 (Rh123), which is transported by P-170. Marked Rh123 efflux was detected in CD8⁺ T lymphocytes with CD8⁺/CD45RA⁺ T cells (naive cells) showing significantly higher P-170 activity as compared with CD8⁺/CD45RA⁻ cells (P < 0.04). Vice versa, CD8⁺/CD45RO⁺ T cells (memory cells) demonstrated less P-170 activity than CD8⁺/CD45RO⁻ cells (P < 0.04). P-170 function was less prominent in CD4⁺ T cells, however, Rh123 efflux was higher in the CD4⁺/CD45RA⁺ and CD4⁺/CD45RO⁻ subpopulations (P < 0.025) corresponding to the CD8⁺ results. Dye efflux differed significantly between activated and non-activated CD8⁺ and CD4⁺ as well as CD8⁺/CD11b⁺ and CD8⁺/CD11b⁻ T lymphocytes. Since CD16⁺ natural killer cells (NK) expressed the highest level of P-170, the NK cytotoxicity against ⁵¹Cr-labelled K562 target cells was assayed in the presence or absence of P-170 inhibitors. NK related cytotoxicity was significantly reduced in the presence of R-verapamil and dexnigaldipine-HCP in a dose-dependent manner.  The differential expression of P-170 activity in naive and memory T cells together with the reduced NK related cytotoxicity in the presence of MDR-modulators suggest a physiological role of P-170 in immunological functions of these lymphocyte subsets. Consequently, the addition of MDR modulators to conventional chemotherapy as a strategy to overcome drug resistance should consider possible adverse immunosuppressive effects.