CMV T Cell Immunity

Cytomegalovirus (CMV), a double-stranded DNA virus, belongs to the Herpesviridae family. The prevalence of CMV infection in adults ranges between 30 and 70%. Following CMV infection the virus spreads hematogenously to almost every organ. CMV then establishes a lifelong latent infection but can reactivate in both immunocompetent and immunocompromised individuals. Clinically significant CMV infection frequently develops in patients who are immunosuppressed because of allogeneic hematopoietic stem cell transplantation (HSCT), solid organ transplantation or HIV infection. In transplant recipients, CMV infection may lead to a higher incidence of graft rejection, opportunistic infections, and decreased allograft and patient survival.

T cell immunity plays a vital role in controlling CMV viral latency. Monitoring of CMV-specific T cell responses assists in the detection of patients at increased risk of CMV disease after transplantation and may be useful in guiding prophylaxis and preemptive therapies. 

Some reference laboratories measure the strength of activity of CD4 and CD8 T cells following stimulation of whole blood with CMV antigens or Staphylococcal enterotoxin B. During incubation Brefeldin A is added, causing interferon (IFN)-gamma to be retained inside the cell. After stimulation cells are recovered and stained for surface markers (CD45, CD3, CD4, CD8, CD69) and intracellular IFN-gamma. They are then analyzed by flow cytometry.

Other reference laboratories measure only CD8 cytotoxic T cell response to CMV. This test assesses the number of CMV-specific CD8 T cells, their ability to produce interferon gamma and their cytotoxic potential using a panel of 5 major histocompatibility complex (MHC) class I alleles (HLA A1, A2, B7, B8, and B35) along with their respective immunodominant CMV epitopes. Cytotoxic potential is measured by the expression of CD107a and CD107b as markers of degranulation.

The report includes total CD3 and CD8 T-cell counts as well as a CMV-specific CD8 T-cell count. The absolute count of CMV-CD8 T cells that are activated and have cytotoxic function in response to specific CMV peptide is also provided.

CMV positive recipients of allogeneic hematopoietic stem cell transplantation and solid organ transplants should have their posttransplant results compared to pretransplant results. Patients with CMV viremia should have their CMV T cell immunity measured as frequently as CMV viral load.

References

Hakki M, Riddell SR, Storek J, et al: Immune reconstitution to CMV after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood 2003;102:3060-3067

Bachier CR: Prevention of early CMV infection in HSCT. Biol Blood Marrow Transplant 2005;15(2):8-9

Boeckh M: Prevention of late CMV infection in HSCT. Biol Blood Marrow Transplant 2005;15(2):9-11

Li CR, Greenberg PD, Gilbert MJ, et al: Recovery of HLA-restricted CMV-specific T cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood 1994;83(7):1971-1979