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© The Rockefeller University Press, 0022-1007/1997/1/251/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 251-262

Articles

Distinct Costimulatory Molecules Are Required for the Induction of Effector and Memory Cytotoxic T Lymphocytes

Yang Liu*, Roland H. Wenger{ddagger}, Min Zhao*, and Peter J. Nielsen{ddagger}

From the * Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, 10016; and the {ddagger} Max Planck Institut für Immunologie, D-79108 Freiburg, Germany

A successful T cell immune response has two major products: effector T cells which directly or indirectly remove the antigens, and memory T cells, which allow a faster and more efficient recall response when challenged by related antigens. An important issue is whether costimulatory molecules on the antigen-presenting cells are involved in determining whether T cells will differentiate into effector or memory cells after antigenic stimulation. To address this issue, we have produced mice with targeted mutations of either the heat-stable antigen (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternative costimulatory pathways for induction of immunological memory to influenza virus. Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells. Our results demonstrate that the induction of memory T cells and effector T cells can utilize distinct costimulatory molecules. These results have important implications on lineage relationship between effector and memory T cells.

Address correspondence to Yang Liu, Department of Pathology, Michael Heidelberger Division of Immunology, NYU Medical Center, 550 First Ave., New York, NY 10016. Dr. Wenger's present address is Physiologisches Institut, University of Zürich, Zürich, Switzerland.

1 Abbreviations used in this paper: CTLp, the precursor for cytolytic lymphocytes; HSA, The heat-stable antigen; WT, wild-type mice; KO, mice with a homozygous targeted-mutation; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein of influenza virus A/JAP.


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