Characterization of the T cell-mediated cellular cytotoxicity during acute infectious mononucleosis

B. E. Tomkinson, Richard Maziarz, J. L. Sullivan

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Abstract

Primary infection with EBV during acute infectious mononucleosis (IM) is associated with a cytotoxic response against allogeneic target cells. C depletion with anti-CD3 (OKT3) and anti-CD8 (OKT8) mAb decreased the allogeneic cytolysis of two EBV-infected lymphoblastoid cell lines (LCL) by 96% and 89%, respectively. Complement depletion with the NK cell-specific mAb Leu-11b and NKH-1a resulted in only a slight decrease (<35%) in the lysis of these LCL. mAb inhibition studies with OKT3 and OKT8 inhibited the allogeneic lysis of two LCL by 87% and 82%, respectively. The alloreactive cytotoxic response was strongly inhibited by mAb specific for MHC class I determinants (W6/32, 65% inhibition and BBM.1, 58% inhibition). Acute IM lymphocytes lysed the allogeneic EBV-negative cell lines HSB2 (45%) and HTLV-1 T cell lines (16%). NK cell-depleted lymphocytes from an acute IM patient demonstrated preferential lysis of K562 transfected with human HLA-A2 (73%) compared with the K562 transfected control (20%). Cold target competition studies with allogeneic and autologous target and competitor LCL demonstrated no significant competitive inhibition between allogeneic and autologous cells. We interpret these results as evidence that 1) the acute IM-alloreactive cytotoxic response is mediated primarily by CTL; 2) these alloreactive CTL lyse allogeneic target cells irrespective of EBV antigenic expression; 3) MHC class I expression is sufficient for allogeneic recognition and lysis of target cells; 4) distinct effector CTL populations mediate lysis of autologous and allogeneic target cells; and 5) during acute IM, EBV infection results in the induction of both virus-specific and alloreactive CTL populations.

Original languageEnglish (US)
Pages (from-to)660-670
Number of pages11
JournalJournal of Immunology
Volume143
Issue number2
StatePublished - 1989
Externally publishedYes

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Infectious Mononucleosis
T-Lymphocytes
Cell Line
Human Herpesvirus 4
Muromonab-CD3
Epstein-Barr Virus Infections
Natural Killer Cells
Lymphocytes
HLA-A2 Antigen
Virus Activation
Human T-lymphotropic virus 1
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Characterization of the T cell-mediated cellular cytotoxicity during acute infectious mononucleosis. / Tomkinson, B. E.; Maziarz, Richard; Sullivan, J. L.

In: Journal of Immunology, Vol. 143, No. 2, 1989, p. 660-670.

Research output: Contribution to journalArticle

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abstract = "Primary infection with EBV during acute infectious mononucleosis (IM) is associated with a cytotoxic response against allogeneic target cells. C depletion with anti-CD3 (OKT3) and anti-CD8 (OKT8) mAb decreased the allogeneic cytolysis of two EBV-infected lymphoblastoid cell lines (LCL) by 96{\%} and 89{\%}, respectively. Complement depletion with the NK cell-specific mAb Leu-11b and NKH-1a resulted in only a slight decrease (<35{\%}) in the lysis of these LCL. mAb inhibition studies with OKT3 and OKT8 inhibited the allogeneic lysis of two LCL by 87{\%} and 82{\%}, respectively. The alloreactive cytotoxic response was strongly inhibited by mAb specific for MHC class I determinants (W6/32, 65{\%} inhibition and BBM.1, 58{\%} inhibition). Acute IM lymphocytes lysed the allogeneic EBV-negative cell lines HSB2 (45{\%}) and HTLV-1 T cell lines (16{\%}). NK cell-depleted lymphocytes from an acute IM patient demonstrated preferential lysis of K562 transfected with human HLA-A2 (73{\%}) compared with the K562 transfected control (20{\%}). Cold target competition studies with allogeneic and autologous target and competitor LCL demonstrated no significant competitive inhibition between allogeneic and autologous cells. We interpret these results as evidence that 1) the acute IM-alloreactive cytotoxic response is mediated primarily by CTL; 2) these alloreactive CTL lyse allogeneic target cells irrespective of EBV antigenic expression; 3) MHC class I expression is sufficient for allogeneic recognition and lysis of target cells; 4) distinct effector CTL populations mediate lysis of autologous and allogeneic target cells; and 5) during acute IM, EBV infection results in the induction of both virus-specific and alloreactive CTL populations.",
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