Cytotoxic T Cells in Cytomegalovirus Infection

Abstract

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.

Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study

“…12,[21][22][23][24] In our study, the use of pre-emptive ganciclovir therapy before day 100 was similar for cases and controls; this factor was thus unlikely to explain the difference in late CMV disease seen in this study. Although continued biweekly surveillance and preemptive therapy was recommended after day 100 for both myeloablative and nonmyeloablative patients, assessing whether surveillance was actually performed was difficult.…”

Effect of host genotype in determining the relative roles of natural killer cells and T cells in mediating protection against murine cytomegalovirus infection

“…As a positive correlation has been observed between the development of significant levels of nonspecific cytotoxic activity and the recovery of bone marrow and renal transplant patients from HCMV disease, the importance of NK cells in controlling HCMV infection should not be underestimated (Quinnan et al, 1982;Bowden et al, 1987;Venema et al, 1994). If there is heterogeneity in the effectiveness of the NK cell response against HCMV, then it may be possible to control HCMV disease in some instances by the adoptive transfer of NK cell clones, or the use of NK cell stimulatory factors.…”

T cell proliferative responses to five human cytomegalovirus proteins in healthy seropositive individuals: implications for vaccine development

“…The importance of the cell-mediated immune response to HCMV in host defence has been well documented (Greenberg et al, 1991a, b;Jonjic et al, 1990 He, C. R. Rinaldo Jr and P. A. Morel et al, 1986;Riddell et al, 1992;Quinnan et al, 1984). Several specific targets for T cell recognition during HCMV infection have been recently identified; these include the envelope glycoprotein gB, the matrix protein pp65 and the immediate early IE1 protein (Liu et al, 1988;Alp et al, 1991;Gilbert et al, 1993).…”

“…It has been shown that both humoral and cell-mediated immunity appear to be involved in the host defence against HCMV infection (Quinnan et al, 1984;Rasmussen, 1990). Convalescent human serum contains antibodies that will react with at least 20 different HCMV proteins, which include capsid, tegument, envelope and non-structural viral proteins.…”