Biomedical subjects

H Mejia Lopez

Publications and source records attributed to H Mejia Lopez.

3 recordsLinked to original sources

PubMed1995

Differential effects of Trypanosoma cruzi on the transcription of the p55IL-2R, c-fos, c-myc and CD69 genes in activated human lymphocytes.

Mitogen-activated lymphocytes co-cultured with either purified Trypanosoma cruzi trypomastigotes or the filtrate of trypomastigote suspensions in culture medium manifest a significant decrease in their capacities to express p55 interleukin-2 receptor molecules (p55IL-2R) on their membrane and proliferate. In this study we found that the cytoplasmic levels of p55IL-2R are also markedly reduced under these conditions. This inhibition appeared to result from altered gene transcription since the levels of p55IL-2R mRNA in phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) dropped substantially in the presence of parasite suspension filtrate. The rates of decay for p55IL-2R mRNA determined in cultures lacking and containing the parasite filtrate after addition of actinomycin D to inhibit further RNA synthesis were comparable. These results indicated that decreased p55IL-2R mRNA was not due to decreased stability of this mRNA under our conditions and pointed to a transcriptional or pre-transcriptional modification as the likely mechanism by which T. cruzi affects activated lymphocytes. The parasite filtrate did not appear to affect transcription of c-fos or c-myc (known to occur in the very early stages of lymphocyte activation) or that of CD69 (which is concomitant with p55IL-2R transcription). Thus, decreased p55IL-2R gene transcription appears to be a somewhat selective effect of a T. cruzi-derived molecule(s) rather than the consequence of an overall shutdown of gene transcription.

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PubMed1995

Trypanosoma cruzi-induced decrease in the level of interferon-gamma receptor expression by resting and activated human blood lymphocytes.

A substantial proportion of human peripheral blood mononuclear cells (PBMC) manifested a decreased capacity to express membrane interferon-gamma receptors (IFN-gamma R) when co-cultured with Trypanosoma cruzi. Among the lymphocytes, B cells accounted for the bulk of this effect, evidenced by a marked drop in the proportion of CD19+ or CD20+ cells expressing IFN-gamma R. Decreased IFN-gamma R expression by B lymphocytes was seen as early as 3 h after co-culture with T. cruzi and persisted for at least 24 h. The parasite had no detectable effect on CD19, CD20 or DR antigen expression by B lymphocytes. Neither the proportion of B cells expressing these markers nor the membrane density of these molecules varied significantly in the presence of T. cruzi. In PBMC cultures stimulated with Staphlyococcus aureus Cowan I (SACI), T. cruzi decreased the percentages of both IFN-gamma R+ and IFN-R+bright (cells expressing above-normal levels of surface IFN-gamma R) B lymphocytes. Cell-free filtrates of T. cruzi suspensions reproduced the suppressive effects of living parasites on IFN-gamma R expression by B cells. When T. cruzi present, the intracellular levels of IFN-gamma R molecules in resting or SACI-activated B lymphocytes, represented by fluorescence intensity, were well below control values, suggesting that decreased surface expression resulted from suppressed IFN-gamma R synthesis. Among T (CD3+) cells, 10.8% to 39.6% (7 donors) expressed surface IFN-gamma R and did so at a very low level. These percentages were also reduced by T. cruzi.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1993

Does interleukin-2 restore lymphocyte responses suppressed by Trypanosoma cruzi?

There has been disagreement about the ability of exogenous interleukin-2 (IL-2) to restore responsiveness to lymphocytes from either Trypanosoma cruzi-infected animals or normal individuals co-cultured with this parasite. The discrepancy has been attributed to the use of different strains of mice or T. cruzi isolates, or to the use of lymphoid cells from different organs. As T. cruzi inhibits the expression of IL-2 receptors by activated lymphocytes in vitro, we were able to test whether restoration of responsiveness by exogenous IL-2 might depend on the level of suppression present in the system. Human or mouse lymphocytes stimulated with phytohaemagglutinin (PHA) exhibited gradual decreases in IL-2 receptor expression, [3H]thymidine incorporation and IL-2 secretion as the concentration of T. cruzi in the culture increased. Exogenous IL-2 afforded a degree of restoration of both IL-2 receptor expression and [3H]thymidine uptake which was substantial at the lower, but very small--if any--at the higher, parasite concentrations tested. Trypanosoma cruzi could not have competed with the lymphocytes for IL-2 because it did not bind significant amounts of this cytokine. These results suggested that the controversy about the corrective effects of IL-2 may be more apparent than real, reflecting variations in the extent of immunosuppression present in different model systems of T. cruzi-associated immunosuppression.

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