The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/4/1193/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 8, April 20, 1998 1193-1204


Articles

T Helper 1 (Th1) and Th2 Characteristics Start to Develop During T Cell Priming and Are Associated with an Immediate Ability to Induce Immunoglobulin Class Switching

Kai-Michael Toellner*, Sanjiv A. Luther{ddagger},§, Daniel M.-Y. Sze*, Richard K.-W. Choy*, Dale R. Taylor*, Ian C.M. MacLennan*, and Hans Acha-Orbea{ddagger},§

From the * Department of Immunology, University of Birmingham Medical School, Birmingham B15 2TT United Kingdom; the {ddagger} Ludwig Institute for Cancer Research, Lausanne Branch; and the § Institute of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland

The respective production of specific immunoglobulin (Ig)G2a or IgG1 within 5 d of primary immunization with Swiss type mouse mammary tumor virus [MMTV(SW)] or haptenated protein provides a model for the development of T helper 1 (Th1) and Th2 responses. The antibody-producing cells arise from cognate T cell B cell interaction, revealed by the respective induction of C{gamma}2a and C{gamma}1 switch transcript production, on the third day after immunization. T cell proliferation and upregulation of mRNA for interferon {gamma} in response to MMTV(SW) and interleukin 4 in response to haptenated protein also starts during this day. It follows that there is minimal delay in these responses between T cell priming and the onset of cognate interaction between T and B cells leading to class switching and exponential growth. The Th1 or Th2 profile is at least partially established at the time of the first cognate T cell interaction with B cells in the T zone.

The addition of killed Bordetella pertussis to the hapten–protein induces nonhapten-specific IgG2a and IgG1 plasma cells, whereas the anti-hapten response continues to be IgG1 dominated. This indicates that a Th2 response to hapten–protein can proceed in a node where there is substantial Th1 activity.


Address correspondence to Kai-Michael Toellner, Department of Immunology, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom. Phone: 44 121 414 6970; Fax: 44 121 414 3599; E-mail: k.m.toellner{at}bham.ac.uk

1 Abbreviations used in this paper: BrdU, 5-bromo-2'-deoxyuridine; CGG, chicken {gamma} globulin; MMTV(SW), Swiss type mouse mammary tumor virus; NP, (4-hydroxy-3-nitrophenyl)acetyl.

The work in Birmingham was supported by a Medical Research Council Programme grant to I.C.M. MacLennan; that in Lausanne was supported by grant number 31-42468.94 from the Swiss National Science Foundation to H. Acha-Orbea. S. A. Luther was funded by the Roche Research Foundation and Emma Muschamp Foundation.


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