Role of CD4 in thymocyte selection and maturation

doi:10.1084/jem.169.6.2085

This Article

	Full Text (PDF, 886K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Zuniga-Pflucker, J. C.
	Articles by Kruisbeek, A. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Zuniga-Pflucker, J. C.
	Articles by Kruisbeek, A. M.

Social Bookmarking

	What's this?

ARTICLES

Role of CD4 in thymocyte selection and maturation

JC Zuniga-Pflucker, SA McCarthy, M Weston, DL Longo, A Singer and AM Kruisbeek
Biological Response Modifiers Program, National Cancer Institute, Bethesda, Maryland 20892.

We examined the possible role of CD4 molecules during in vivo and in vitro fetal thymic development. Our results show that fetal thymi treated with intact anti-CD4 mAbs fail to generate CD4 single-positive T cells, while the generation of the other phenotypes remains unchanged. Most importantly, the use of F(ab')2 and Fab anti-CD4 mAb gave identical results, i.e., failure to generate CD4+/CD8- T cells, with no effect on the generation of CD4+/CD8+ T cells. Since F(ab')2 and Fab anti-CD4 fail to deplete CD4+/CD8- in adult mice, these results strongly argue that the absence of CD4+/CD8- T cells is not due to depletion, but rather, is caused by a lack of positive selection, attributable to an obstructed CD4-MHC class II interaction. Furthermore, we also observed an increase in TCR/CD3 expression after anti-CD4 (divalent or monovalent) mAb treatment. The TCR/CD3 upregulation occurs in the double-positive population, and may result from CD4 signaling after mAb engagement, or may be a consequence of the blocked CD4-class II interactions. One proposed model argues that the CD3 upregulation occurs in an effort to compensate for the reduction in avidity or signaling that is normally provided by the interaction of the CD4 accessory molecule and its ligand. As a whole, our findings advocate that CD4 molecules play a decisive role in the differentiation of thymocytes.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Stephens, G. L., Ashwell, J. D., Ignatowicz, L. (2003). Mutually antagonistic signals regulate selection of the T cell repertoire. Int Immunol 15: 623-632 [Abstract] [Full Text]
Zhan, Y., Purton, J. F., Godfrey, D. I., Cole, T. J., Heath, W. R., Lew, A. M. (2003). Without peripheral interference, thymic deletion is mediated in a cohort of double-positive cells without classical activation. Proc. Natl. Acad. Sci. USA 100: 1197-1202 [Abstract] [Full Text]
Vermeire, K., Bell, T. W., Choi, H.-J., Jin, Q., Samala, M. F., Sodoma, A., De Clercq, E., Schols, D. (2003). The Anti-HIV Potency of Cyclotriazadisulfonamide Analogs Is Directly Correlated with Their Ability to Down-Modulate the CD4 Receptor. Mol. Pharmacol. 63: 203-210 [Abstract] [Full Text]
Herzyk, D J, Bugelski, P J, Hart, T K, Wier, P J (2002). Practical aspects of including functional endpoints in developmental toxicity studies. Case study: immune function in HuCD4 transgenic mice exposed to anti-CD4 MAb in utero. Hum Exp Toxicol 21: 507-512 [Abstract]
Adachi, S., Amasaki, Y., Miyatake, S., Arai, N., Iwata, M. (2000). Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation. J. Biol. Chem. 275: 14708-14716 [Abstract] [Full Text]
Bugelskil, P J, Herzykl, D J, Rehm, S, Harmsen, A G, Gore, E V, Williams, D M, Maleeff, B E, Badger, A M, Truneh, A, O'Brien, S R, Macial, R A, Wier, P J, Morgan, D G, Hart, T K (2000). Preclinical development of keliximab, a PrimatizedTM anti-CD4 monoclonal antibody, in human CD4 transgenic mice: characterization of the model and safety studies. Hum Exp Toxicol 19: 230-243 [Abstract]
Yelon, D., Schaefer, K. L., Berg, L. J. (1999). Alterations in CD4-Binding Regions of the MHC Class II Molecule I-Ek Do Not Impede CD4+ T Cell Development. J. Immunol. 162: 1348-1358 [Abstract] [Full Text]
Zhang, X.-L., Seong, R., Piracha, R., Larijani, M., Heeney, M., Parnes, J. R., Chamberlain, J. W. (1998). Distinct Stage-Specific cis-Active Transcriptional Mechanisms Control Expression of T Cell Coreceptor CD8{alpha} at Double- and Single-Positive Stages of Thymic Development. J. Immunol. 161: 2254-2266 [Abstract] [Full Text]
Frank, G. D., Parnes, J. R. (1998). The Level of CD4 Surface Protein Influences T Cell Selection in the Thymus. J. Immunol. 160: 634-642 [Abstract] [Full Text]
Bendelac, A, Killeen, N, Littman, D., Schwartz, R. (1994). A subset of CD4+ thymocytes selected by MHC class I molecules. Science 263: 1774-1778 [Abstract]
Sebzda, E, Wallace, V., Mayer, J, Yeung, R., Mak, T., Ohashi, P. (1994). Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science 263: 1615-1618 [Abstract]
van Meerwijk, J., Germain, R. (1993). Development of mature CD8+ thymocytes: selection rather than instruction?. Science 261: 911-915 [Abstract]
Marrack, P., Blackman, M., Burgert, H.-G., McCormack, J.M., Cambier, J., Finkel, T.H., Kappler, J. (1989). T-cell Repertoire and Thymus. Cold Spring Harb Symp Quant Biol 54: 105-110 [Abstract]
Zuniga-Pflucker, J.C., Jones, L.A., Longo, D.L., Kruisbeek, A.M. (1989). Both TCR/MHC and Accessory Molecule/MHC Interactions Are Required for Positive and Negative Selection of Mature T Cells in the Thymus. Cold Spring Harb Symp Quant Biol 54: 153-158 [Abstract]