ANALYSIS OF PERIPHERAL-BLOOD LYMPHOCYTE POPULATIONS AND IMMUNE FUNCTION FROM CHILDREN EXPOSED TO CYCLOSPORINE OR TO AZATHIOPRINE IN-UTERO

We have analyzed PBL from 7 children exposed to CsA in utero and 4 chi ldren exposed to AZA in utero. Expression of CD3, CD4, CD8, and CD20 w ere normal for both groups of children; however, significant differenc es were detected in the expression of CD45RA, CD45RO, and CD29. While CsA-exposed children had higher density of CD45RA, and a higher propor tion of CD45RA(+)RO(-) T cells, than did unexposed children, those exp osed to AZA alone had decreased CD45RA(+) and a large increase in CD45 RA(-)RO(+) T cells. It appears the exposure to CsA slightly delays T c ell development, whereas exposure to AZA, without concomitant exposure to CsA, accelerates development to that of an adult. The effects of C sA abrogated the effects of AZA when both were present during pregnanc y. The expression of CD29, the beta 1-integrin, on T cells has been li nked to enhanced ability to respond to recall antigens and to home to sites of infection. Among children exposed to CsA, T cells from cord b lood and a 8-month-old infant have a normal CD29 profile. However from 1 to 6 years of age the proportion of T cells expressing a high densi ty of CD29 is significantly lower (4-fold) than that of T cells from u nexposed children. Because these children have no outward signs of imm unodeficiency, we postulate that this low proportion is still sufficie nt for normal immune responsiveness. The distribution of CD29 on T cel ls was different for the 3 study groups. Among CsA-exposed children, a lthough the proportion of CD29(hi) T cells was much reduced, all were CB45RA(+), as was also the case for unexposed children. In contrast, a mong children exposed only to AZA the majority of CD29(hi) T cells wer e CD45RO(+). Serological testing indicated that immunoglobulin and com plement levels, as well as seroconversion in response to vaccination, were normal among CsA-exposed children, with no detectable autoantibod ies to cellular or tissue components, including parietal cells. Unlike T cell development in inbred rodents, the immune system in humans app ears to be remarkably resilient, and successfully adapts to the presen ce of CsA during its early developmental stages. This work. suggests t hat the presence of CsA throughout pregnancy has only a minimal effect on fetal immune development and appears to have less impact on T cell s than does exposure to AZA only. We conclude that children exposed to CsA in utero are not likely to be at risk. of immunodeficiency or aut oimmunity.