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Alloreactive T Cells That Do Not Require TCR and CD8 Coengagement Are Present in Naive Mice and Contribute to Graft Rejection¹

Pamela A. Smith^*, and Terry A. Potter^2,*,

^* Division of Basic Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206; and the Department of Immunology and the Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262

Class I alloreactive CTL populations have been defined as either CD8 dependent or CD8 independent, based upon their ability to kill target cells in the presence of Ab to CD8. The CD8-dependent population uses CD8 in a coreceptor role with the TCR, and mutations in the class I molecule that destroy the CD8 binding site abrogate CTL killing, even if the target cell expresses other allelic forms of class I molecules with an intact binding site for CD8. The CD8-independent population apparently does not require CD8, as Ab to CD8 has no effect on the ability of these cells to kill appropriate target cells. We have isolated a third population of CTL that is inhibited by the addition of CD8 Ab yet can kill target cells that express the alloantigenic molecule incapable of binding CD8, provided that the target cells also express non antigenic class I molecules that contain an intact binding site for CD8. We refer to these cells as CD8 bystander-dependent CTL. Many (10 of 12) of these CTL were able to kill H-2K^b-expressing transfectants of T2 cells, consistent with the idea that they recognize a peptide-independent determinant that may be expressed at a high density on the cell surface. These CD8 bystander-dependent CTL are only readily detectable in vitro when spleen cells from mice primed in vivo with a skin graft are used.