Human T-cell cultures from virus-sensitized donors can mediate virus-specific and HLA-restricted cell lysis

Abstract

Human cells infected with viruses such as herpes simplex virus (HSV) or Epstein–Barr virus (EBV) become susceptible to the lytic action of a distinct population of lymphocytes termed natural killer (NK) cells present in the blood of normal (sero-negative) and sero-positive individuals^1,2. Although NK cells probably represent a subset within the T-cell lineage^3,4, they are apparently not restricted in their lytic activity by the major histocpmpatibility complex (MHC) determinants as are most cytotoxic T lymphocytes (CTLs; ref. 5), but can potentially lyse a variety of unrelated virus-infected⁶ or uninfected cultured cells^4,7. In studies with murine models, it has been demonstrated that HSV^8,9 or murine cytomegalovirus (MCMV) specific^10,11 CTLs show the phenomenon of H–2 restriction initially described by Doherty and Zinkernagel with the LCM virus system¹², which is that the CTLs and targets must share H–2K or H–2D products. However, studies in man have not demonstrated the existence of HSV- or human cytomegalovirus (HCMV)-specific CTLs showing HLA (human analogue of mouse H–2) restriction in their lytic activity towards virally infected targets. We demonstrate here that T cells from the peripheral blood of patients recently cured of HSV or HCMV infections, when triggered in vitro with specific antigen and grown as long-term cultures in the presence of T-cell growth factor (TCGF), can mediate virus-specific and HLA-restricted lysis of virus-infected targets. We believe this to provide the first evidence that HLA-restricted and virus-specific T-cell mediated cytotoxicity can be demonstrated in human–HSV and HCMV systems. These HSV- or HCMV-specific CTLs could be important in limiting the in vivo spread of the respective viruses and/or in the pathogenesis of the disease caused by them.