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J Virol, June 1998, p. 4866-4873, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Vaccine-Induced, Pseudorabies Virus-Specific, Extrathymic CD4+CD8+ Memory T-Helper Cells in Swine

Bertram T. Ober,1 Artur Summerfield,2 Christina Mattlinger,1 Karl-Heinz Wiesmüller,3 Günther Jung,4 Eberhard Pfaff,1 Armin Saalmüller,1,* and Hanns-Joachim Rziha1

Federal Research Centre for Virus Diseases of Animals1 and Institut für organische Chemie, Universität Tübingen,4 D-72076 Tübingen, and Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, D-72762 Reutlingen,3 Germany, and Institute for Virology and Immunoprophylaxis, CH-3147 Mittelhaeusern, Switzerland2

Received 29 October 1997/Accepted 17 February 1998

Pseudorabies virus (PRV; suid herpesvirus 1) infection causes heavy economic losses in the pig industry. Therefore, vaccination with live attenuated viruses is practiced in many countries. This vaccination was demonstrated to induce extrathymic virus-specific memory CD4+CD8+ T lymphocytes. Due to their major histocompatibility complex (MHC) class II-restricted proliferation, it is generally believed that these T lymphocytes function as memory T-helper cells. To directly prove this hypothesis, 15-amino-acid, overlapping peptides of the viral glycoprotein gC were used for screening in proliferation assays with peripheral blood mononuclear cells of vaccinated d/d haplotype inbred pigs. In these experiments, two naturally processed T-cell epitopes (T1 and T2) which are MHC class II restricted were identified. It was shown that extrathymic CD4+CD8+ T cells are the T-lymphocyte subpopulation that responds to epitope T2. In addition, we were able to show that cytokine secretion can be induced in these T cells through recall with inactivated PRV and demonstrated that activated PRV-primed CD4+CD8+ T cells are able to induce PRV-specific immunoglobulin synthesis by PRV-primed, resting B cells. Taken together, these results demonstrate that the glycoprotein gC takes part in the priming of humoral anti-PRV memory responses. The experiments identified the first T-cell epitopes so far known to induce the generation of virus-specific CD4+CD8+ memory T lymphocytes and showed that CD4+CD8+ T cells are memory T-helper cells. Therefore, this study describes the generation of virus-specific CD4+CD8+ T cells, which is observed during vaccination, as a part of the potent humoral anti-PRV memory response induced by the vaccine.

* Corresponding author. Mailing address: Bundesforschungsanstalt für Viruskrankheiten der Tiere, Paul-Ehrlich Strasse 28, 72076 Tübingen, Germany. Phone: 49-7071-967256. Fax: 49-7071-967303. E-mail: armin.saalmueller{at}tue.bfav.de.

J Virol, June 1998, p. 4866-4873, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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