The Mortimer M. Bortin lecture Robert L. Truitt  Biology of Blood and Marrow Transplantation  Volume 10, Issue 8, Pages 505-523 (August 2004) DOI: 10.1016/j.bbmt.2004.05.005

Figure 1 Evolution of models used by the author to describe the relationship between GVL and GVH reactivity over the past 3 decades. A, Model circa 1975 (R. Truitt, unpublished data). At issue was whether the GVL effect of allogeneic BMT was separable from GVHD. If distinct (or overlapping) cell populations were responsible, then it might be possible to have a GVL reaction without GVHD. B, Model circa 1985 [88]—the clonal basis for GVL and GVH reactivity was established. Distinct effector cells capable of leukemia-specific killing were identified, including NK/LAK cells (“C”) and antigen-specific T cells (“D”). Some allospecific CTL clones caused GVHD (“A”), but others did not (“B”). The importance of cytokines in the activation and clonal expansion of GVL-specific effector cells was established (arrow). C, Model circa 1995 [287]—the relative contributions of CD4+ and CD8+ T cells to GVHD were now well established. Cytokines were important for activation and clonal amplification of GVL effector cell populations (arrows), but they were also implicated in the pathophysiology of acute and chronic GVHD. The dichotomy of CD4+ T-helper (Th) cell function was identified along with the principle of reciprocal cross-regulation by Th1 and Th2 cytokines (expanded boxes). Some allospecific CD8+ cytotoxic T-cell clones (Tc) caused lethal GVHD, whereas others did not. Secretion of cytokines (tumor necrosis factor [TNF] and interleukin-2 [IL-2]) was thought to account for the strong GVH reactivity of some Tc clones because lytic activity did not correlate with GVHD. Leukemia-specific T-cell clones were identified, including MHC-restricted and non-MHC-restricted CTLs. The latter seemed to be leukemia specific because they recognized allogeneic MHC class Ib molecules present on leukemia but with limited tissue distribution on normal tissues (ie, Qa-1–specific CTLs). Biology of Blood and Marrow Transplantation 2004 10, 505-523DOI: (10.1016/j.bbmt.2004.05.005)