T-CELLS SPECIFIC FOR A POLYMORPHIC SEGMENT OF CD45 INDUCE GRAFT-VERSUS-HOST DISEASE WITH PREDOMINANT PULMONARY VASCULITIS

To study the character of graft-vs-host disease (GVHD) induced by T ce lls specific for hemopoietic cells, T cells specific for a polymorphic segment of CD45 were transferred into CD45 congenic mice, C57BL/6 mic e that express the CD45b allele were immunized with a 13 mer peptide r epresenting the polymorphic segment (p(257-268)) of CD45a protein. Con versely, C57BL/6 mice congenic for CD45a were immunized with the CD45b peptide. CD4(+) T cells specific for allelic CD45 peptides were elici ted. Importantly, T cells specific for CD45 peptides proliferated spec ifically and vigorously in response to spleen cells expressing the app ropriate polymorphic CD45 protein. T cells specific for CD45 induced a substantial graft-vs-host response (GVHR) with predominant early pulm onary vasculitis and later more widespread interstitial mononuclear ce ll infiltration and alveolitis, No GVHR was induced in bone marrow chi meras expressing only donor hemopoietic cells. Thus, donor T cell reco gnition of host hemopoietic cells is sufficient to elicit GVHR, but th e classical skin, liver, and gut manifestations of GVHD were not obser ved. The CD45-specific T cells used secreted Th1 cytokines, but withou t detectable soluble IL-2, Studies using CD45-specific T cells with di fferent effector functions might allow further dissection of donor cel l requirements for GVHD syndromes.