Intraallograft chemokine RNA and protein during rejection of MHC-matched/multiple minor histocompatibility-disparate skin grafts

Chemokines direct leukocyte recruitment into sites of tissue inflammation a nd may facilitate recruitment of leukocytes into allografts following trans plantation. Although the expression of chemokines during rejection of MHC-d isparate allografts has been examined, chemokine expression in MHC-matched/ multiple minor histocompatibility Ag-disparate allografts has not been test ed. The intraallograft RNA expression of several C-X-C and C-C chemokines w as tested during rejection of full thickness skin grafts from B10.D2 donors on control Ig-, anti-CD4 mAb-, and anti-CDS mAb-treated BALB/c recipients. In all recipients, two patterns of intragraft chemokine expression were ob served during rejection of these grafts: 1) macrophage-inflammatory protein -1 alpha, macrophage-inflammatory protein-1 beta, GRO-alpha (KC), JE, and I FN-gamma-inducible protein (IP-10) were expressed at equivalent levels in a llo- and isografts for 2-4 days posttransplant and then returned to low or undetectable levels; and 2) IP-10 and monokine induced by IFN-gamma (Mig) w ere expressed in the allografts 3 days before rejection was completed, sugg esting a possible role in recruiting primed T cells into the allograft, Thr ee days before completion of rejection, intraallograft IP-10 protein was re stricted to the epidermis, whereas Mig was located in the lower dermis and associated with the intense infiltration of mononuclear cells. Treatment of B10.D2 recipients with rabbit antiserum to Mig, but not to IP-10, delayed rejection of the allografts 3-4 days. The results suggest that Mig mediates optimal recruitment of T cells into MHC-matched/multiple minor histocompat ibility Ag-disparate allografts during rejection.