Biomedical subjects

L P Fernandez

Publications and source records attributed to L P Fernandez.

3 recordsLinked to original sources

PubMed1995

Does thalidomide affect IL-2 response and production?

The exact mechanism of immunosuppression by thalidomide is poorly understood. A common denominator in the pathogenesis of graft-vs.-host disease, graft rejection, reactional lepromatous leprosy, and autoimmune disorders modulated by thalidomide is the activation of T lymphocytes culminating in the synthesis of interleukin-2 (IL-2), the expression of high-affinity IL-2 receptors, and the induction of proliferation. We investigated the effect of thalidomide on the production of IL-2 by the human leukemia cell line Jurkat through induction of IL-2 gene enhancer activity and through the presence of IL-2 in supernatants. beta-galactosidase activity, encoded by a reporter lac z construct and controlled by a transcription factor in thalidomide-treated PMA- and ionomycin-stimulated Jurkat cells, was similar (97 +/- 1.33%; p > 0.1) to non-thalidomide-treated controls at all drug concentrations tested. IL-2 enhancer-driven beta-galactose activity of thalidomide-treated and stimulated cells was also similar to that of untreated controls (p > 0.2). The IL-2 production of activated nontransfected Jurkat cells was gauged by using the IL-2-dependent cell line HT-2 as a readout and by ELISA. Jurkat cells were subcloned by limiting dilution. Bulk cultures and three subclones (J.5.2.5., J.5.2.9., and J.5.3.8.) were assayed at 6, 12, and 24 hours after PHA/PMA-induced stimulation. No inhibitory effect on the IL-2 production by thalidomide could be detected at any of the drug concentrations tested (5-30 micrograms/mL), whereas 10 to 100 ng/mL of cyclosporine inhibited the IL-2 production by 95 to 100%. In addition, we observed neither inhibition of IL-2-dependent proliferation of HT-2 nor inhibition of PHA-induced proliferation of peripheral mononuclear cells by thalidomide at all drug concentrations used (5-30 micrograms/mL). These results do not support the possibility of a modulatory effect on the immune response by thalidomide via IL-2 production and IL-2 response.

Cells, Cultured↗

PubMed1994

Prevention of graft-versus-host disease by peptides binding to class II major histocompatibility complex molecules.

Graft-versus-host disease across minor histocompatibility barriers was induced in two different models by transplanting allogeneic bone marrow and spleen cells into irradiated H-2-compatible recipient mice. In this report, we show that administration of peptides with high binding affinity for the respective class II major histocompatibility complex molecules after transplantation is capable of preventing the development of graft-versus-host disease in two different murine models. The peptides used were myelin basic protein residues 1 through 11 with alanine at position 4 (Ac 1-11[4A]) for I-Au (A alpha uA beta u), and the antigenic core sequence 323 through 339 of ovalbumin with lysine and methionine extension (KM core) for I-As (A alpha sA beta s). In both systems, the mechanism of prevention was found to be major histocompatibility complex-associated, because nonbinding control peptides did not have any effect. Engraftment of allogeneic bone marrow cells was shown by polymerase chain reaction analysis of DNA polymorphisms in a microsatellite region within the murine interleukin-5 gene.

Amino Acid Sequence↗

PubMed1993

Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells.

Cytokine-induced killer (CIK) cells are highly efficient cytotoxic effector cells capable of lysing tumor cell targets. Cultures of human CIK cells have been shown to have enhanced cytotoxicity and to proliferate more rapidly than lymphokine activated killer (LAK) cells by both in vitro and in vivo studies. In this report, we have further characterized the phenotype of CIK cells and explored the molecular structures involved in CIK-mediated cell lysis of tumor target cells. The dominant cell phenotype in CIK cell cultures expresses the alpha, beta T cell receptor (TCR-alpha/beta). In addition, CD56 is expressed on the main effector cell on a per-cell basis. Interestingly, the total number of CD56+ cells increases more than 1000-fold during the generation of CIK cells, mainly due to expansion of CD56+ cells coexpressing CD3. The higher lytic activity of CIK cells as compared to LAK cells is mainly due to the higher proliferation of CD3+CD56+ cells and to the cytotoxic activity of TCR-alpha/beta+ cells in CIK cell cultures. CIK-mediated cellular lysis is non-major histocompatibility antigen (MHC) restricted. The cytotoxic effect of CIK cells against tumor targets is blocked by antibodies directed against lymphocyte function-associated antigen (LFA-1) and its counter receptor, intercellular adhesion molecule-1 (ICAM-1).

Animals↗