A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo.

The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed naïve precursors is firmly established. Th1 cells are characterized by IFN production and, in mice, the selective switching to IgG2a. Conversely IL-4 production and selective switching to IgG1 and IgE characterize Th2 cells. Analysis of Th2 inductionin vitroindicates that this polarization develops gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely anti-CD3 and IFN induce Th1 cells. In this report, we explore evidence that indicates that the T helper cell polarizationin vivocannot solely be explained by the cytokine environment. This is provided by studying the early acquisition of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing antigens. It is shown that these divergent forms of T cell help can rapidly develop in cells within a single lymph node. It is argued that early polarization to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate interaction between virgin T cells and dendritic cells, in the absence of type 1 or type 2 cytokines. This contrasts with the critical role of the cytokines in reinforcing the Th-phenotype and selectively expanding T helper clones.

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The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels

International Journal of Nanomedicine ◽

10.2147/ijn.s37465 ◽

2013 ◽

pp. 351 ◽

Cited By ~ 11

Author(s):

Ingrid Hilger ◽

Franke ◽

Kettering ◽

Lange ◽

Kaiser

Keyword(s):

Multidrug Resistance ◽

Iron Oxide ◽

Protein Expression ◽

Cancer Cells ◽

Mitomycin C ◽

Iron Oxide Nanoparticles ◽

Oxide Nanoparticles ◽

Multidrug Resistance Protein ◽

Expression Levels ◽

Resistance Protein

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Polymorphism in PfMRP1 (Plasmodium falciparum Multidrug Resistance Protein 1) Amino Acid 1466 Associated with Resistance to Sulfadoxine-Pyrimethamine Treatment

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00091-09 ◽

2009 ◽

Vol 53 (6) ◽

pp. 2553-2556 ◽

Cited By ~ 37

Author(s):

Sabina Dahlström ◽

M. Isabel Veiga ◽

Andreas Mårtensson ◽

Anders Björkman ◽

J. Pedro Gil

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Antimalarial Activity ◽

Intermittent Preventive Treatment ◽

Genetic Alterations ◽

Multidrug Resistance Protein ◽

Nucleotide Polymorphisms ◽

Resistance Protein ◽

Selection Of

ABSTRACT Sulfadoxine-pyrimethamine (SP) remains widely recommended for intermittent preventive treatment against Plasmodium falciparum malaria for pregnant women and infants in Africa. Resistance to SP is increasing and associated primarily with mutations in the P. falciparum dhfr (Pfdhfr) and Pfdhps genes. This study aimed to explore the hypothetical association of genetic alterations in the P. falciparum multidrug resistance protein gene (Pfmrp1) with the in vivo response to SP by detecting the selection of single nucleotide polymorphisms (SNPs) following standard single-dose treatment administered to children with acute uncomplicated P. falciparum malaria in Tanzania. We detected significant selection of parasites carrying the Pfmrp1 1466K allele in samples from children with recrudescent infections, with 12 (100%) of 12 such samples being positive for this allele, compared to 52 (67.5%) of 77 baseline samples (P = 0.017), in parallel with the selection of the Pfdhfr Pfdhps quintuple mutant haplotype in cases of recrudescence (P = 0.001). There was no association between the 1466K SNP and the Pfdhfr Pfdhps quintuple mutation, indicating independent selections. Our data point for the first time to a role for a P. falciparum multidrug resistance protein homologue in the antimalarial activity of SP. Moreover, they add to the growing evidence of the potential importance of Pfmrp1 in antimalarial drug resistance.

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Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells.

Journal of Experimental Medicine ◽

10.1084/jem.168.2.543 ◽

1988 ◽

Vol 168 (2) ◽

pp. 543-558 ◽

Cited By ~ 251

Author(s):

R Fernandez-Botran ◽

V M Sanders ◽

T R Mosmann ◽

E S Vitetta

Keyword(s):

Proliferative Response ◽

Th2 Cells ◽

Th1 Cells ◽

T Helper ◽

T Helper 1 ◽

Ifn Gamma ◽

T Helper 2 ◽

Regulatory Interactions ◽

Th Cell ◽

Th1 And Th2

Murine Th1 and Th2 subsets differ not only in the lymphokines they produce, but also functionally. It is not clear what factors influence the preferential activation of one subset versus the other and what regulatory interactions exist between them. The purpose of this study was to examine the effect of lymphokines produced by clones of Th1 cells (IL-2 and IFN-gamma), Th2 cells (IL-4), and APC (IL-1) on the proliferative response of Th1 and Th2 cells after antigenic stimulation. Activation of both types of clones in the presence of antigen and APC resulted in the acquisition of responsiveness to the proliferative effects of both IL-2 and IL-4, although Th2 cells were more responsive to IL-4 than Th1 cells. Responsiveness of Th1 and Th2 cells to both lymphokines decreased with time after initial antigenic activation; Th1 cells lost their responsiveness to IL-4 more rapidly and to IL-2 more slowly than Th2 cells. IFN-gamma partially inhibited the IL-2 and IL-4-mediated proliferation of Th2, but not Th1 cells. Although the presence of IL-1 was not required for the response of Th1 or Th2 cells to IL-4, its presence resulted in a synergistic effect with IL-2 or IL-4 in Th2 but not in Th1 cells. Both subsets responded to a mixture of IL-2 and IL-4 in synergistic fashion. Delayed addition and wash-out experiments indicated that both IL-2 and IL-4 had to be present simultaneously in order for synergy to occur. These results suggest that Th cell subsets might regulate each other via the lymphokines that they secrete and that the pathways of IL-2 and IL-4 mediated proliferation are interrelated.

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Distinct Role of Antigen-Specific T Helper Type 1 (Th1) and Th2 Cells in Tumor Eradication in Vivo

Journal of Experimental Medicine ◽

10.1084/jem.190.5.617 ◽

1999 ◽

Vol 190 (5) ◽

pp. 617-628 ◽

Cited By ~ 296

Author(s):

Takashi Nishimura ◽

Kenji Iwakabe ◽

Masashi Sekimoto ◽

Yasushi Ohmi ◽

Takashi Yahata ◽

...

Keyword(s):

Cell Therapy ◽

Th2 Cells ◽

T Helper ◽

Th1 Cell ◽

Th2 Cell ◽

Tumor Eradication ◽

Th1 And Th2

The role of T helper type 1 (Th1) and Th2 cells in tumor immunity was investigated using Th cells induced from ovalbumin (OVA)-specific T cell receptor transgenic mice. Although Th1 cells exhibited stronger cytotoxicity than Th2 cells, both cell types completely eradicated tumors when transferred into mice bearing A20 tumor cells transfected with the OVA gene (A20-OVA). Th1 cells eradicated the tumor mass by inducing cellular immunity, whereas Th2 cells destroyed the tumor by inducing tumor necrosis. Both Th1 and Th2 cells required CD8+ T cells to eliminate tumors, and neither of these cells were able to completely eliminate A20-OVA tumors from T and B cell–deficient RAG2−/− mice. Mice cured from tumors by Th1 and Th2 cell therapy rejected A20-OVA upon rechallenge, but CD8+ cytotoxic T lymphocytes were induced only from spleen cells prepared from cured mice by Th1 cell therapy. Moreover, we demonstrated that Th1 and Th2 cells used distinct adhesion mechanisms during tumor eradication: the leukocyte function-associated antigen (LFA)-1–dependent cell–cell adhesion step was essential for Th1 cell therapy, but not for Th2 cell therapy. These findings demonstrated for the first time the distinct role of antigen-specific Th1 and Th2 cells during eradication of established tumors in vivo.

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