RESTRICTED V-BETA USAGE BY T-CELLS INFILTRATING REJECTING HUMAN LUNG ALLOGRAFTS

TCR expression was evaluated in lung transplant patients to determine whether T cells infiltrating rejecting lung allografts employed restri cted V beta elements. Serial bronchoalveolar lavage (BAL) specimens we re obtained from six lung transplant recipients at approximately 3 wk, 6 wk, and 3 mo post-transplant. T cell lines were established by cult uring lavage cells with irradiated donor splenocytes in the presence o f low dose IL-2 for 3 wk, and TCR V beta usage was determined by quant itative reverse transcriptase-PCR. Patients were grouped into three ca tegories based on TCR V beta profiles and the clinical status of the a llograft. 1) In one patient, BAL-derived T cells expressed heterogeneo us V beta repertoires at all time points evaluated. This patient did n ot experience graft rejection during the 16-mo period of observation, though respiratory infections were diagnosed. 2) In three patients, V beta usage by BAL-derived T cells was restricted during allograft reje ction episodes, but was heterogeneous in the absence of rejection and during respiratory infections. In one of these patients, similar V bet a repertoires were employed by BAL cells during multiple rejection epi sodes. 3) In two patients, restricted V beta usage by BAL-derived T ce lls was observed before and during rejection episodes. Collectively, t hese data illustrate that human lung allograft rejection, but not pulm onary infection, is associated with T cells expressing a limited numbe r of V beta families. Restricted V beta usage by graft-reactive T cell s may allow for the selective elimination of these cells using TCR-spe cific reagents, thereby promoting allograft-specific tolerance.