EFFECTS OF PREGNANCY ON LYMPHOCYTES WITHIN SHEEP UTERINE INTERPLACENTOMAL EPITHELIUM

PROBLEM: Previous studies demonstrate increases in the number and gran ularity of gamma delta T cells within the sheep uterine interplacentom al epithelium during pregnancy. To further characterize their activati on and function, gamma delta T-cell receptor (TCR)(+) intraepithelial lymphocytes (IELs) from nonpregnant and pregnant uteri were phenotyped extensively. Cytokine mRNA expression in the epithelium and by gamma delta TCR+ IELs isolated from pregnant uteri was also examined. METHOD OF STUDY: Cell suspensions were prepared from the uterine interplacen tomal epithelium and from the peripheral blood of nonpregnant and preg nant ewes (120-140 days of gestation). Surface marker expression was d etermined by two-color flow cytometry and cytokine expression determin ed by reverse transcriptase-polymerase chain reaction. RESULTS: Uterin e gamma delta TCR+ IELs exhibited increased beta 1-integrin expression but decreased leukocyte function associated antigen (LFA)-1 and major histocompatibility complex class I expression during pregnancy. Major histocompatibility complex class II, CD44, CD2, and LFA-3 expression was unchanged during pregnancy, whereas CD25, VLA-4 and L-selectin wer e never expressed. The same cytokines were expressed in the pregnant a nd nonpregnant uterine interplacentomal epithelium with detectable mRN A for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and i nterleukin (IL)-1 alpha, but not for IL-2 or IL-4. gamma delta TCR+ an d CD8(+) IEL purified from pregnant uteri expressed mRNA for IFN-gamma , TNF-alpha, transforming growth factor-beta, and IL-10. CONCLUSIONS: gamma delta TCR+ IELs from pregnant uteri have cytoplasmic granules, a nd express CD8 and cytokines indicative of cytotoxic potential. Phenot ypic changes induced during pregnancy differed from those observed aft er activation of circulating naive cells and may represent further sti mulation of fully differentiated effecters. gamma delta TCR+ IELs are present only in interplacentomal areas of pregnant uteri and may contr ol trophoblast invasion within these areas.