Activation of Lymphocytes by HHV-6 Antigen in Normal Children and Adults

Abstract

We investigated the immune reaction of lymphocytes in response to human herpes virus-6 (HHV-6) in normal children and adults. Cell proliferation was assayed by measurement of the incorporation of 5-bromo-2'-deoxyuridine (BrdU) by enzyme-linked immunosorbent assay (ELISA), and changes in expression of interleukin-2 receptors (IL-2Rs) (alpha-, beta3-, and gamma-chain) were assayed by flow cytometry. Incorporation of BrdU and expression of IL-2Rs (alpha-, beta-, and gamma-chain) in CD4+, CD8+, and CD45RO+ lymphocytes were increased when peripheral blood mononuclear cells (PBMC) from HHV-6 seropositive children aged 3 to 12 years and adults were cultured with HHV-6 antigen compared with control antigen. In contrast, cord blood mononuclear cells (CBMC) and PBMC from seronegative children did not show cell proliferation and changes in expression of IL-2Rs. In seropositive children less than 2 years of age, the magnitude of cell proliferation was low and IL-2Rs (alpha-, beta-, and gamma-chain) in CD8+ cells and IL-2Rs (alpha-chain) in CD45RO+ cells were increased. These data suggest that children below the age of 2 had immature lymphocytic response to HHV-6 antigen. Deletion of monocytes from PBMC and the addition of a mixture of anti-IL-2Rs (alpha-, beta-, and gamma-chain) antibodies reduced cell proliferation in response to HHV-6, suggesting the requirement of the presence of monocytes and expression of IL-2Rs.

Human CD4+T Cell Response to Human Herpesvirus 6

“…Early studies established T cell proliferative responses to HHV-6 in most healthy adults (69,81,87). Subsequent studies using peripheral blood mononuclear cells (PBMCs) have demonstrated T cell responses by both CD4 ϩ and CD8 ϩ T cells (24,40,77). However, HHV-6-specific T cell clones and T cell lines (TCLs) have been established only for CD4 ϩ T cells (40,42,69,80,81,87).…”

“…Subsequent studies using peripheral blood mononuclear cells (PBMCs) have demonstrated T cell responses by both CD4 ϩ and CD8 ϩ T cells (24,40,77). However, HHV-6-specific T cell clones and T cell lines (TCLs) have been established only for CD4 ϩ T cells (40,42,69,80,81,87). The fine specificity of the T cell response to HHV-6 is largely unexplored.…”

HHV-6 Specific T-Cell Immunity in Healthy Children and Adolescents

“…After primary infection, human herpes viruses establish a lifelong latent infection in the host and persist in certain host cells. Latently infected cells may express virus-specific antigens on their cell surface ( 15 , 17 ). However, to protect themselves from immuno-recognition, human herpes viruses have a limited viral gene expression during latency ( 13 ).…”

Immune response to HHV-6 and implications for immunotherapy

“…The virus can reactivate under conditions of deficient cell-mediated immunity [20]. Although immunity to HHV-6B could evolve over time, there is evidence that lifelong responses to HHV-6B are imprinted very early after the first onset of HHV-6B infection [21]. Neonates are usually protected from HHV-6B infection by maternal-derived antibodies until titers wane over 3–9 months after birth, making older children susceptible to infection [22].…”