Cytotoxic T Cells in Cytomegalovirus Infection: HLA-Restricted T-Lymphocyte and Non-T-Lymphocyte Cytotoxic Responses Correlate with Recovery from Cytomegalovirus Infection in Bone-Marrow-Transplant Recipients

We studied 58 recipients of bone-marrow transplants to evaluate immune responses to cytomegalovirus infection. Such infection developed in 43 patients; it was fatal in 12, nonfatal in 23, and present at death from other causes in eight. All patients had low or absent cytomegalovirus-specific cytotoxic lymphocyte activity before the onset of infection. Cytomegalovirus-specific cytotoxic responses developed in all survivors, whereas only two patients with fatal infection had even low-level cytomegalovirus-specific cytotoxic responses. Natural and antibody-dependent killer-cell activities were depressed both before and during infection in patients with fatal infections, but not in those who survived. The outcome of the infection did not correlate with the nature of the underlying disease, the type of transplant received, the pretransplantation cytomegalovirus-antibody status, or lymphocyte-proliferation responses to cytomegalovirus antigens or concanavalin A. The correlation between effective virus-specific cytotoxic response and recovery from infection indicates that these effector cells probably mediate recovery from cytomegalovirus infection. (N Engl J Med. 1982; 307:6–13.) THE importance of cytomegalovirus (CMV) as a human pathogen relates to its propensity to produce disease in persons with impaired or immature cellular immune responsiveness. Such diseases include congenital mental retardation 1 and serious disseminated infection in recipients of bone-marrow, 2 renal, 3 and cardiac 4 allografts. More than half of all bone-marrow-transplant recipients acquire CMV infections — which are often fatal — regardless of the presence of serum antibodies, but the cellular responses that mediate recovery are unknown. 5 , 6 Studies of CMV-antigen-specific in vitro lymphocyte-transformation responses have not demonstrated a correlation with the outcome of infection. 6 In contrast, in a murine model, evidence has . . .