Constant IFNgamma mRNA to protein ratios in cord and adult blood T cells suggests regulation of IFNgamma expression in cord blood T cells occurs at the transcriptional level.

Low levels of IFNgamma produced by umbilical cord blood (UCB) T lymphocytes upon activation may be due to the need for a high threshold of activation or to intrinsic blocking transcription/translation. We examined IFNgamma mRNA accumulation and protein expression in pharmacologically stimulated human UCB and adult blood (AB) T cells. Our data indicate that both IFNgamma mRNA accumulation and protein synthesis were significantly lower in stimulated UCB T cells than the AB T cells. Since the RNA dependent kinase PKR, an inhibitor of translation, can be activated by low levels of IFNgamma mRNA, we measured its involvement. Treatment with 2-amino-purine, an inhibitor of PKR, did not enhance IFNgamma protein expression in UCB T cells. Furthermore, our studies indicated that IFNgamma promoter hypermethylation does not appear to regulate IFNgamma expression either, as treatment with the demethylating agent, 5-aza-2'-deoxycytidine, did not lead to a significant increase in IFNgamma mRNA accumulation in UCB T cells. What is readily evident from our studies is that the IFNgamma mRNA to protein ratio was similar in UCB and AB T cells and it was not altered by any of the treatments used. These results therefore suggests that IFNgamma expression in UCB T cells is suppressed at the transcriptional level by an unknown mechanism(s).