Role of CD4 in thymocyte selection and maturation - PubMed (original) (raw)
Role of CD4 in thymocyte selection and maturation
J C Zuñiga-Pflücker et al. J Exp Med. 1989.
Abstract
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.
Similar articles
- CD8 is required during positive selection of CD4-/CD8+ T cells.
Zúñiga-Pflücker JC, Jones LA, Longo DL, Kruisbeek AM. Zúñiga-Pflücker JC, et al. J Exp Med. 1990 Feb 1;171(2):427-37. doi: 10.1084/jem.171.2.427. J Exp Med. 1990. PMID: 1968084 Free PMC article. - Effects of in vivo administration of anti-CD3 monoclonal antibody on T cell function in mice. II. In vivo activation of T cells.
Hirsch R, Gress RE, Pluznik DH, Eckhaus M, Bluestone JA. Hirsch R, et al. J Immunol. 1989 Feb 1;142(3):737-43. J Immunol. 1989. PMID: 2521507 - The co-receptor function of murine CD4.
Janeway CA Jr, Rojo J, Saizawa K, Dianzani U, Portoles P, Tite J, Haque S, Jones B. Janeway CA Jr, et al. Immunol Rev. 1989 Jun;109:77-92. doi: 10.1111/j.1600-065x.1989.tb00020.x. Immunol Rev. 1989. PMID: 2670749 Review. No abstract available. - Molecular biology and function of CD4 and CD8.
Parnes JR. Parnes JR. Adv Immunol. 1989;44:265-311. doi: 10.1016/s0065-2776(08)60644-6. Adv Immunol. 1989. PMID: 2493728 Review. No abstract available.
Cited by
- Human immunodeficiency virus gp120 binding C'C" ridge of CD4 domain 1 is also involved in interaction with class II major histocompatibility complex molecules.
Moebius U, Clayton LK, Abraham S, Diener A, Yunis JJ, Harrison SC, Reinherz EL. Moebius U, et al. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12008-12. doi: 10.1073/pnas.89.24.12008. Proc Natl Acad Sci U S A. 1992. PMID: 1465431 Free PMC article. - The role of CD4 in regulating homeostasis of T helper cells.
König R, Shen X, Maroto R, Denning TL. König R, et al. Immunol Res. 2002;25(2):115-30. doi: 10.1385/IR:25:2:115. Immunol Res. 2002. PMID: 11999166 Review. - Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex.
Glassman CR, Parrish HL, Lee MS, Kuhns MS. Glassman CR, et al. Cell Rep. 2018 Jan 30;22(5):1263-1275. doi: 10.1016/j.celrep.2017.12.104. Cell Rep. 2018. PMID: 29386113 Free PMC article. - Role of CD4 molecule in intrathymic T-cell development.
Takeuchi Y, Horiuchi T, Hamamura K, Sugimoto T, Yagita H, Okumura K. Takeuchi Y, et al. Immunology. 1991 Oct;74(2):183-90. Immunology. 1991. PMID: 1836198 Free PMC article. - Evaluation of the functional equivalence of major histocompatibility complex class II A and E complexes.
Cosgrove D, Bodmer H, Bogue M, Benoist C, Mathis D. Cosgrove D, et al. J Exp Med. 1992 Aug 1;176(2):629-34. doi: 10.1084/jem.176.2.629. J Exp Med. 1992. PMID: 1500864 Free PMC article.
References
- Nature. 1977 Sep 29;269(5627):417-8 - PubMed
- J Exp Med. 1989 May 1;169(5):1619-30 - PubMed
- Immunology. 1978 Aug;35(2):317-31 - PubMed
- Immunol Rev. 1979;47:63-90 - PubMed
- J Exp Med. 1980 Aug 1;152(2):280-95 - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials