T-cell responses to predicted amphipathic peptides of varicella-zoster virus glycoproteins II and IV

Abstract

Four peptides from the predicted amino acid sequences of varicella-zoster virus (VZV) glycoproteins II and IV selected for potential amphipathicity and a terminal lysine residue were synthesized. The peptides elicited weak proliferative responses by T cells with the CD4+ UCHL1+ CD45Rphenotype from the blood of VZV-immune individuals. The frequency of responder cells in individuals with specific response to peptides was 1:80,000 or fewer blood mononuclear cells, and the number of peptides responded to did not correlate with the proliferative response to VZV antigen. Of 40 peptide-specific T-cell clones obtained by limiting dilution, 10 were restimulated by extracted VZV antigen in the presence of autologous antigen-presenting cells. A total of 50% of these clones lysed HLA class II-positive lymphoblasts which had been preincubated with the appropriate peptide, and 2 of 15 cytotoxic clones lysed lymphoblast targets superinfected with VZV. The data indicated that T cells with specificity for putative VZV peptides may readily be cultured from the subset of blood mononuclear cells which bears the phenotype associated with memory.

Depressed immune functions in the early phase of varicella‐zoster virus reactivation

“…The presence of antibodies is not sufficient to prevent VZV reactivation, and increased incidence of herpes zoster has been correlated with age, burden of malignancy, administration of immunosuppressants, and im-Saibara et al pairment of cell-mediated immunity. Thus, cell-mediated immunity is believed to play a n important role in the host defenses against VZV [Diaz et al, 1989;Duby et al, 1989;Giller et al, 1989;Grose, 1989;Watson et al, 1990;Hayward, 1990;Arvin et al, 1991;Sharp et al, 19921. VZV reactivation could be induced by impairment of the host's cell-mediated immune system; however, there is no report on the immune state during the early stage of VZV reactivation.…”

“…Our study has also shown that the depressed immune functions improve gradually during the recovery phases. This finding is in accord with the clinical course of herpes zoster, because it is usually a self-limiting disease and cellular immunity to VZV has been demonstrated in vitro in patients who recovered from herpes zoster and in vaccinated patients [Russel et al, 1972;Patel et al, 1978;Diaz et al, 1989;Duby et al, 1989;Giller et al, 1989;Grose, 1989;Watson et al, 1990;Hayward, 1990;Arvin et al, 1991;Sharp et al, 19921. The results suggest three possible mechanisms for depressed immune functions; 1) a temporary decrease in T-cell mediated immune response through other acute viral infections or undetected malignancies, 2) a temporary decrease in T-cell mediated pathogen-specific immune response [Reed et al, 19721, and 3) a transient fluctuation of T-cell mediated immunity as VZV replication could occur even in immunocompetent subjects. Obvious fluctuations of gamma-IFN production, LAK activity, or NK activity were not detected in the 40 healthy volunteers whose immune functions were assessed every week over 4 months.…”

“…Children with agammaglobulinemia and hypogammaglobulinemic patients without detectable antibody against VZV recover from varicella-zoster in a normal clinical course [Good and Zak, 1956;Stevens and Merigan, 19721 and the presence of specific antibodies to VZV is not necessarily sufficient to prevent reactivation of VZV [Brunell and Gershon, 19751. These data suggest the importance of the cellular immune response to VZV [Russel et al, 1972;Diaz et al, 1989;Duby et al, 1989;Giller et al, 1989; Grose, 1989;Watson et al, 1990;Hayward, 1990;Arvin et al, 1991;Sharp et al, 19921. Gamma-interferon (IFN) production by peripheral mononuclear cells (PBMC) has been shown to be the major inhibiting factor of VZV replication [Rabalais et al, 19891 and to be useful for predicting the time of recurrence of herpes labialis [Cunningham and Merigan, 19831. Furthermore, the assessment of gamma-IFN production and lymphokine activated killer (LAK) cell activity is helpful in the detection of defects in the function of cell-mediated immunity I Saibara et al, 1989, 19901.…”

Varicella-zoster virus

“…IE62 protein and gE epitopes are immunogenic in individuals of diverse major histocompatibility complex (MHC) class II phenotypes. T-lymphocyte recognition of amphipathic regions of gB and gI, some of which exhibit helper B-cell function, have also been detected with VZV-specific CD4 ϩ T-lymphocyte clones from immune individuals (123).…”

“…As in the case of humoral immunity, T lymphocytes from healthy immune subjects recognize many proteins made by VZV ( Table 2). While it has not been possible to examine responses to the 69 or more gene products of the virus, several glycoproteins and the IE62 major tegument/regulatory protein are known targets of the cell-mediated immune response to VZV (9,13,102,123). T-lymphocyte responses to gE, gH, and the IE62 protein are elicited during primary VZV infection in the immunocompetent host, although the sequence in which T-lymphocyte recognition of these proteins develops is variable.…”