Effect of phorbol myristate acetate (PMA) and ionophore A23187 on interleukin-2 levels and proliferation of activated T lymphocytes from patients with lepromatous leprosy.
The immunodeficiency present in patients with lepromatous leprosy is characterized by the limited proliferation of T lymphocytes, and is explained in part by the impaired synthesis of interleukin-2 (IL-2). Diacylglycerol (DAG) and calcium produce the activation of PKC, ERK and JNK kinases, implying a normal IL-2 response. Phorbol esters, such as PMA, can substitute for DAG and are mitogenic to human T and B cells activating several cytokine-encoding genes. Ionophore A23187 increases calcium permeability across the cellular membrane to the cytosol of lymphoid cells and is considered a co-mitogen of T lymphocytes. Here we report that: 1) PHA-activated T lymphocytes from LL patients can be separated in vitro into two groups: a) responders (R) with a stimulation index (SI) of > 10 and (b) nonresponders (NR) with a SI of < 10. 2) The proliferative responses of cells from LL(R), LL(NR) and normal subjects were measured after being stimulated with: I, PHA, PMA, PMA + I PHA + PMA and PHA + PMA + ionophore (PPI). The most important result occurs in LL(NR) patients whose cells did not respond to PHA stimulation but increased to normal levels of proliferation when they were stimulated with PMA. Furthermore, the three groups, (NR, R and normals) strongly increased their responses when they were incubated with PPi. 3) Finally, Il-2 concentrations in the supernatants of cultures of T lymphocytes from LL(NR), LL(R) and controls were relatively low when they were incubated with PHA or PMA, but the addition of ionophore to PMA and the combination of PHA + PMA strongly increased the production of IL-2 in all of them, reaching the optimum IL-2 concentration when PPI is used. It can be concluded that the use of PMA, analogous to DAG, and ionophore A23187 (calcium increaser) in cultures of mitogen-activated T lymphocytes from LL patients induced the expression of the IL-2 gene, thus correcting the inadequate proliferation of T cells from LL patients.
Alfaro-Bustamante
F
F
Departamento Biologia Celular y Molecular, Universidad de Guadalajara, Jalisco, Mexico.
Ramirez-Flores
G
G
Gonzalez-Mendoza
A
A
Islas-Rodriguez
A
A
Fafutis-Morris
M
M
D000328:Adult; D000368:Aged; D000001:Calcimycin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D015440:Leprosy, Lepromatous / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007376:Interleukin-2; D010835:Phytohemagglutinins; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate