Open AccessAbsence of Epstein‐Barr virus‐specific, HLA class II‐restricted CD4 + cytotoxic T lymphocytes in infectious mononucleosis
Author(s) -
ENSSLE K. H.,
FLEISCHER B.
Publication year - 1990
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1990.tb08104.x
Subject(s) - ctl* , cytotoxic t cell , biology , immunology , cd8 , antigen , mhc class i , virology , major histocompatibility complex , human leukocyte antigen , epstein–barr virus , virus , in vitro , biochemistry
SUMMARY Cytotoxic T lymphocytes (CTL) with the CD4 + phenotype that recognize major histocompatibility complex (MHC) class II antigens are detectable very frequently in cultures of human alloreactive or virus‐specific T cells. The significance of these CD4 + CTL for an immune reaction in vivo is not clear, Since Epstein‐Barr virus (EBV) transformed B cells express HLA‐class I and class II antigens equally well both CD8 + and CD4 + CTL should be stimulated during an acute EBV infection. We analysed the MHC specificity and the phenotype of EBV‐specific CTL from patients with infectious mononucleosis (IM). When tested directly without any previous culture, T cells from patients in the acute phase of IM showed specific MHC‐restricted cytotoxicity against the autologous B cell line. Addition of a HLA class I specific monoclonal antibody (MoAb) but not of a HLA class II specific MoAb resulted in a complete blocking of the lytic activity. Cell sorting revealed that the entire cyloloxic activity was present in the CD8 + fraction whereas no specific CTL were detectable in the CD4 + fraction. The absence of cytotoxicity in CD4 + cells was not due to a lack of activation of these cells since both CD8 + and CD4 + cells were activated in situ , showing spontaneous growth in interleukin‐2 (IL‐2) and expressing the activation marker TP103. Frequency estimation revealed that 1/300‐1/600 CD8 + but only 1/2000‐1/4000 CD4 + T cells gave rise to a specific CTL colony after 10 days. If CD4 + colonies were tested repeatedly for cytotoxicity we found that CD4 + CTL acquired their cytotoxicity during in vitro culture. In addition, we isolated EBV‐specific CD4 T cell clones able to lyse their stimulator cells in the presence but not in the absence of leclin even after a long period of culture. Taken together our results show that cytotoxicity mediated by CD4 + T cells does not play a role in an anti‐viral immune response.