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Journal of Virology, July 2002, p. 6602-6608, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6602-6608.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Expansion of a CD28-Intermediate Subset among CD8 T Cells in Patients with Infectious Mononucleosis

Hiroshi Uda,1 Toru Mima,1 Norihiko Yamaguchi,1 Yoshinori Katada,1 Masayuki Fukuda,1 Naohiko Fujii,1 Kojiro Nakamura,2 and Osamu Saiki1*

Department of Clinical Investigation, Osaka-Minami National Hospital, Kido-Higashi, Kawachi-Nagano City, Osaka 586,1 Department of the Central Laboratory, Osaka University Medical School at the Research Institute for Microbial Disease, Suita, Osaka 565, Japan2

Received 21 December 2001/ Accepted 9 April 2002

Infectious mononucleosis (IM) is an acute sporadic infection that usually affects young adults, and during infection a massive expansion of CD8 T cells is generally considered to occur. However, CD28 expression of the expanded cells has not been characterized. When peripheral blood mononuclear cells of acute IM (AIM) patients were analyzed by flow cytometry, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28 negative, intermediate (int), and positive, was seen for CD8 T cells. We studied 26 IM patients who were diagnosed on the basis of standard methods and found that all patients had the continuous CD28 spectrum. CD28 is a costimulatory molecule on T cells, and its expression is associated with the subdivision of CD8 cells into cytotoxic (CD28-positive) and suppressor (CD28-negative) T cells. After 24 h of ex vivo culturing, however, the continuous spectrum was found to consist of only CD28-positive and CD28-negative CD8 T cells, because the CD28-int cells had disappeared due to apoptosis. The CD28-int T cells have several cytotoxic functions, suggesting that CD28-int T cells are effectors. Examination of other costimulatory markers in AIM patients showed that CD80 and CD152 were not affected. In patients with other viral infections, such as measles or rubella, however, the continuous spectrum was not detected. These results suggest that there is an unusual CD28 expression pattern in patients with AIM, namely, the presence of a functional CD28-int subset among CD8 T cells. These findings are of special importance for clarifying the defense mechanism against Epstein-Barr virus infection, and the role of CD28 molecules in humans and should also be helpful for the diagnosis of AIM.


* Corresponding author. Mailing address: Department of Clinical Investigation, Osaka Minami National Hospial, Kido-Higashi Cho 2-1, Kawachi-Nagano City, Osaka 586-8521, Japan. Phone: 81-721-53-5761. Fax: 81-721-53-8904. E-mail: osaiki{at}jun.ncvc.go.jp.


Journal of Virology, July 2002, p. 6602-6608, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6602-6608.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.