Impact of Persistent Cytomegalovirus Infection on Dynamic Changes in Human Immune System Profile

Abstract

Human cytomegalovirus (HCMV) imprints the immune system after primary infection, however its effect during chronic infection still needs to be deciphered. In this study we report the variation of blood cell count along with anti-HCMV IgG and T cell responses to pp-65 and IE-1 antigens, that occurred after an interval of five years in a cohort of 25 seropositive healthy adults. We found increased anti-viral IgG antibody responses and intracellular interferon-gamma secreting CD8+ T cell responses to pp-65: a result consistent with memory inflation. With the only exception of shortage in naive CD8+ T cells most memory T cell subsets as well as total CD8+ T cells, T cells, lymphocytes, monocytes and leukocytes had increased. By contrast, none of the cell types tested were found to have increased in 14 subjects stably seronegative. Rather, in addition to a shortage in naive CD8+ T cells, also memory T cell subsets and most other cell types decreased, either in a statistically significant or non-significant manner. The trend of T cell pool representation with regard to CD4/CD8 ratio was in the opposing directions depending on HCMV serology. Globally, this study demonstrates different dynamic changes of most blood cell types depending on presence or absence of HCMV infection. Therefore, HCMV plays a continual role in modulating homeostasis of blood T cells and a broader expanding effect on other cell populations of lymphoid and myeloid origin.

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

“…IgG antibody inflation in MCMV infection was observed and high-dose infection was associated with the presence of neutralizing antibodies [106]. Importantly, an "inflationary" B cell response that gradually increases IgG levels to high frequencies was found in the persistent phase of HCMV infection [107]. This may indicate that CMV vectors may be exploited to induce not only an expanding T-cell response but also a life-long humoral immune protection against vectored antigens.…”

The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer

“…The circulating T‐cell pool is characterized by the expansion of memory T cells after recovery from primary infection; significant differences persist between seronegative and seropositive subjects . Most memory T cells, particularly CD8 + T cells, monocytes as well as leucocytes, are increased in seropositive healthy adults after an interval of 5 years, whereas naive/precursor CD8 + T cells are decreased . CMV‐specific CD4 + and CD8 + T cells can also dominate the memory compartment of seropositive humans .…”

“…Furthermore, the effector‐memory T‐cell pool of CMV‐specific T cells varies among individuals and seems to correlate with the memory CD8 + T‐cell pool size . The opposing trends between two groups of individuals (CMV serostatus +/−) showed that the change of the CD4/CD8 ratio over time may be influenced by CMV infection; the former was significantly reduced in CMV‐seropositive individuals but it was increased in seronegative individuals …”

“…9,52,53 Most memory T cells, particularly CD8 + T cells, monocytes as well as leucocytes, are increased in seropositive healthy adults after an interval of 5 years, whereas naive/precursor CD8 + T cells are decreased. 54 CMV-specific CD4 + and CD8 + T cells can also dominate the memory compartment of seropositive humans. 7 Furthermore, the effector-memory T-cell pool of CMV-specific T cells varies among individuals and seems to correlate with the memory CD8 + T-cell pool size.…”

“…55,56 The opposing trends between two groups of individuals (CMV serostatus +/À) showed that the change of the CD4/CD8 ratio over time may be influenced by CMV infection; the former was significantly reduced in CMV-seropositive individuals but it was increased in seronegative individuals. 54 In contrast, most inflationary cells in MCMV-infected mice fail to sustain their numbers through homeostatic or antigen-driven division and are programmed to perish, even in the presence of chronic CMV infection. MCMVspecific T cells do not undergo homeostatic division and have a relatively poor proliferative potential.…”