Occurrence and Mechanisms

The occurrence, nature, and pathogenesis of intestinal lesions were studied in a number of graft vs. host reaction (GVHR) conditions in mice, combining variations in the nature of the following: the F1 hosts (newborn or adult, normal or lethally irradiated), the injected parental T cells (mixed or selected subsets of Lyt2' or L3T4' cells), and the antigenic stimulus (semiallogeneic or restricted to class I or II MHC loci). The following conclusions were drawn: (a) Three gut alterations are always associated: (i) donor T cell infiltration, predominating in the crypt region; (it) acceleration of the epithelium renewal; and (ifi) increased epithelial Ia expression. (b) The initial event is T-cell infiltration, which results from stimulation within the Peyer patches followed by cyclic traffic, i.e., migration into the thoracic duct and then seeding to the whole gut mucosa. (c) Both Lyt2' and L3T4' cells can infiltrate the gut wall, the extent of the infiltration by a given subset depending upon (i) the capacity of the donor blasts to circulate in the thoracic duct (higher for L3T4+) and then to home in the gut (much higher for Lyt2' blasts) and (it) the nature of the alloantigenic stimulation that governs the extent of each donor subset proliferation. (d) Both donor T-cell subsets can induce gut epithelial damage, but for a comparable amount of infiltrating cells, L3T4' cells induce more lesions. (e) When the antigenic stimulation is restricted to class I or class I MHC loci, gut GVHR is much more easily elicited across class II MHC differences, which stimulate preferentially L3T4' donor cells. (f ) The main mechanism of epithelial damage is not direct cytotoxicity, but more probably lymphokine(s) release.