However, together they have synergistic or additive inhibitory effects as demonstrated by the (i) increased amount of inflammatory cytokines/granzyme B secreted by the CD8+ T cells from the double knockout mice as compared with the single knockout cells, (ii) changes in the recruitment of SHP1 and SHP2 in the single knockout mice, (iii) enhanced autoimmunity in the double knockout mice [16] and elevated antitumor activity by the combinatorial antibody blockade (Figure 3, [12]). The gene discussed is CD8A; the disease is Autoimmunity.