HIGH IL-4 PRODUCING pHTL FREQUENCY IS CORRELATED WITH REDUCED INCIDENCE OF HEART ALLOGRAFT REJECTION.
Els Van Hoffen¹, Margee Robertus¹, Elske Polen¹, Corinne Kl"pping², Frits Gmelig-Meyling³ and Roel De Weger¹, University Hospital, Utrecht, The Netherlands.


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Acute heart allograft rejection occurs most frequently during the first months after transplantation. After 6-12 months, hardly any acute rejection episode is observed. This is correlated with a donor-specific non-responsiveness, which is reflected in a reduced frequency of donor-specific cytotoxic T-cell precursors (pCTL) in peripheral blood lymphocytes (PBL). Because CTL are regulated by helper T-cells (HTL), we questioned whether the reduced pCTL frequency was correlated with a reduction in the frequency of either IL-2 or IL-4 producing HTL. We measured the precursor frequency of HTL before and at several time points after transplantation, in PBL of 10 recipients, using Limiting Dilution Analysis (LDA) for IL-2 and IL-4. In most patients, HTL frequencies dropped immediately after transplantation, to 30-40% of pre-HTX values. This was correlated with a drop in the number of T-cells due to the immunosuppression. In most patients, the frequencies recovered to pre-HTX values at time points longer after transplantation. For IL-2, no correlation was observed between pre-HTX pHTL frequencies and the rejection score. No difference was observed between patients who suffered from acute rejection episodes requiring additional treatment, versus patients who did not suffer from such rejection episodes. For IL-4 however, the pHTL frequencies before transplantation were significantly higher in patients who did not suffer from rejection episodes, compared to patients who did. This phenomenon was not donor-specific, but was also observed against third party cells. In conclusion, patients who have a high frequency of allo-reactive IL-4 producing pHTL, seem to have a reduced incidence of acute rejection episodes after heart transplantation. The high frequency of IL-4 producing cells is not donor-specific, and may have a genetic background. This may have a beneficial effect in down-regulating the production of IL-2 and IFN , thereby suppressing the induction of a rejection response.