IL-7 TRANSGENIC MICE - ANALYSIS OF THE ROLE OF IL-7 IN THE DIFFERENTIATION OF THYMOCYTES IN-VIVO AND IN-VITRO

We have generated a high copy number transgenic mouse line in which ex pression of mouse IL-7 cDNA is under the control of the mouse MHC clas s II E(alpha) promoter, These mice were generated in order to see if I L-7 over-production in the thymus altered either thymocyte differentia tion or the process of negative selection, Using in site hybridization , IL-7 transcripts could be detected in the thymic cortex and medulla as well as the spleen and lymph nodes of transgenic mice but was undet ectable in normal controls, Phenotypic and molecular analysis of thymo cytes from embryonic and adult transgenic mice failed to reveal a dram atic effect of IL-7 on thymocyte differentiation and negative selectio n of the TCR V-beta repertoire appeared to be intact, In peripheral ly mph nodes, there was a massive (30-fold) increase in the number of T c ells (CD8(+) > CD4(+)) and simultaneous presence of immature (B220(+), Ig(-)) B cells, TCR repertoire analysis showed that the expansion of peripheral T cells was polyclonal. Using the polymerase chain reaction (PCR), transgene-specific IL-7 transcripts could be detected in the t hymus from day 14 of fetal development, However, using semi-quantitati ve PCR, there was no dramatic increase in the degree of TCR beta or TC R alpha gene rearrangements during thymocyte ontogeny in vivo, Similar ly, when fetal mouse thymus lobes were cultured with IL-7 in vitro, th ere was no dramatic increase in the degree of TCR beta or TCR alpha ge ne rearrangements, We conclude that IL-7 is probably not an important differentiation factor for immature mouse thymocytes.