International Immunology, Vol. 11, No. 5, 845-857,
May 1999
© 1999 Japanese Society for Immunology
Generation of antigen-specific cytotoxic T lymphocytes and regulation of cytokine production takes place in the absence of CD3
1 Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
2 Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
3 Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02215, USA
4 Department of Cellular Biology and Immunology, Instituto de Parasitologia y Biomedicina, Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain
Correspondence to: C. Terhorst
The TCR-associated protein CD3
plays a major role in regulating the state of responsiveness to peptide–MHC complexes on the surface of antigen-presenting cells. In this paper the requirement of CD3 in the generation of cytotoxic T cells was compared with its requirement in cytokine gene activation in two mutant mice: ZKO mice with a disrupted CD3 gene and ZTG mice in which a truncated CD3 segment was expressed as a transgene on the ZKO background. Upon infection of ZTG mice with lymphocytic choriomeningitis virus (LCMV), antigen-specific cytotoxic T lymphocyte (CTL) responses were detected, identical to responses in wild-type mice. In addition, antigen-specific CTL responses to allogeneic class I and class II MHC in ZTG animals were indistinguishable from those in wild-type animals. However, CTL responses to the same major antigens were not detectable in ZKO mice. We conclude that the signal transduction pathways leading to CTL development and cytokine production can be triggered through TCR in the absence of functional CD3, provided the remainder of the TCR–CD3 complex is expressed at high levels on the cell surface. Surprisingly, IFN-
production in response to LCMV followed the same kinetics in ZKO, ZTG and wild-type mice. However, in vitro studies showed that cytokine production in general was abnormally regulated in T lymphocytes from ZKO mice, in contrast to ZTG T cells. Taken together, these studies support the hypothesis that development of CTL can take place in the absence of functional CD3. However, CTL development requires stronger TCR-initiated signal transduction events than induction of cytokine genes.
Keywords: cytokines, cytotoxicity, infectious immunity virus, TCR, transgenic/knockout
Transmitting editor: J. Kearney
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. J. Natuk, D. Cooper, M. Guo, P. Calderon, K. J. Wright, F. Nasar, S. Witko, D. Pawlyk, M. Lee, J. DeStefano, et al. Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4+ Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge J. Virol., May 1, 2006; 80(9): 4447 - 4457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Grabert, L. P. Cousens, J. A. Smith, S. Olson, J. Gall, W. B. Young, P. A. Davol, and L. G. Lum Human T Cells Armed with Her2/neu Bispecific Antibodies Divide, Are Cytotoxic, and Secrete Cytokines with Repeated Stimulation Clin. Cancer Res., January 15, 2006; 12(2): 569 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Appel, L. Gauthier, J. Pyrdol, and K. W. Wucherpfennig Kinetics of T-cell Receptor Binding by Bivalent HLA-DR{middle dot}Peptide Complexes That Activate Antigen-specific Human T-cells J. Biol. Chem., January 7, 2000; 275(1): 312 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ulivieri, A. Peter, E. Orsini, E. Palmer, and C. T. Baldari Defective Signaling to Fyn by a T Cell Antigen Receptor Lacking the alpha -Chain Connecting Peptide Motif J. Biol. Chem., January 26, 2001; 276(5): 3574 - 3580. [Abstract] [Full Text] [PDF]
|
|