Platelet-activating factor plays a role in the mechanism of major histocompatibility complex in T lymphocytes

In recent studies, using a swine model of single lung transplantation, we d emonstrated that IRT alone increased MHC II expression in the host's periph eral T lymphocytes. The inhibition of increased MHC II expression with TCV- 309, a specific platelet-activating factor (PAF) antagonist suggested that PAF might play a role in the mechanism of increased MHC II expression. The purpose of the current study was two fold: 1) to investigate the mechanism of PAF-induced increased expression of MHC II in T lymphocytes, 2) to deter mine whether a specific PAF-antagonist, TCV-309, is capable of inhibiting t he increased expression in an in vitro system. This study was subdivided, u sing four in vitro conditions: 1) purified resting T cells, 2) purified pro liferating T cells, 3) PBL treated with PAF, and 4) PBL preincubated with T CV-309 and treated with PAF. The level of MHC II on T cells were measured b y two color flow cytometry analysis (swine anti-CD3, MHC II-DR-beta antibod ies). Both MHC II intensity and the number of CD3(+)MHC(+) T cells did not change in resting purified T cells once treated with PAF. Furthermore, MHC II int ensity did not change in purified proliferating T cells treated with PAF. T he number of CD3(+)MHC(+) T cells, however, increased significantly (p<0.05 ) from day 1 to day 4 as compared with pre-treatment value (day 0) for puri fied proliferating T cells. Treatment of PBL with PAF (10(-7)M) resulted in a significant (p<0.05) increase in MHC II expression from day 2 to day 4 p ost-treatment. The number of CD3(+)MHC(+) T cells in PBL, however, did not change significantly upon treatment with PAF. The results of this study indicated that PAF did not have a direct effect o n increased MHC II expression in resting or proliferating purified T lympho cytes. However, the mechanism of PAF-induced increased expression of MHC II in T cells may be via an indirect pathway involving accessory cells. TCV-3 09, a specific PAF receptor antagonist, is capable of inhibiting this PAF-i nduced increased expression of MHC II in T cells.