DIFFERENTIAL REQUIREMENT OF CD28 COSTIMULATION FOR ACTIVATION OF MURINE CD8(-NODE CELLS() INTESTINAL INTRAEPITHELIAL LYMPHOCYTE SUBSETS ANDLYMPH)

The CD8(+)CD4(-) (CD8(+)) murine small intestinal intraepithelial lymp hocytes (IELs) contain two subpopulations, one expressing alpha alpha- CD8 homodimers and another alpha beta-CD8 heterodimers, In this study, plate-bound anti-TCR beta-chain (TCR-beta) mAb alone or combined with anti-CD28 mAb is used as a model system to study activation requireme nt of these two CD8(+) IEL subsets, In contrast to CD8(+) lymph node ( LN) cells that require both TCR and CD28 triggering for activation, al pha beta-CD8(+) IELs proliferate and produce IL-2 and IFN-gamma when s timulated with anti-TCR-beta mAb alone, and soluble CTLA-4 Ig has no e ffect on their responses. On the other hand, alpha alpha-CD8(+) IELs n either make IL-2 or IFN-gamma nor proliferate even when both stimuli a re provided, However, alpha alpha-CD8(+) IELs are capable of prolifera tion to a similar extent as alpha beta-CD8(+) IELs in the presence of exogenous IL-2. The frequency of cells capable of proliferation in bot h CD8(+) IEL subsets is lower than in CD8(+) LN cells, which contribut es to the weaker and delayed response of CD8(+) IELs.