Journal article
Kinetics of anti-CD4-induced T helper cell depletion and inhibition of function. Activation of T cells by the CD3 pathway inhibits anti-CD4-mediated T cell elimination and down-regulation of cell surface CD4
The Journal of immunology (1950), Vol.148(6), pp.1613-1619
03/15/1992
DOI: 10.4049/jimmunol.148.6.1613
PMID: 1347302
Abstract
In vivo treatment with anti-CD4 antibody profoundly suppresses a number of T cell-dependent responses and is clinically useful in the treatment of certain mouse models of autoimmune disease. Treatment with anti-CD4 antibody will inactivate and can deplete CD4 T cells, but the mechanisms responsible for these effects are incompletely understood. When mouse spleen cells were exposed in vitro to both SRBC and monoclonal anti-CD4, there was 55% reduction of the anti-SRBC response. If cultures were preincubated with anti-CD4 for 48 h before in vitro challenge, the reduction was greater than 80%. When unfractionated spleen cells were cultured with anti-CD4 for 96 h, there was actual elimination of CD4 cells in these cultures since virtually all CD3+ cells were CD8+. Activation of T cells by exposure to anti-CD3 rendered them resistant to antibody-mediated CD4 depletion. This resistance to CD4 depletion was seen even in cultures that were pretreated with anti-CD4 for as long as 24 h before anti-CD3 exposure. In cultures of purified T cells, anti-CD4 did not eliminate CD4 T cells. However, culture of T cells with macrophage-rich adherent cells and anti-CD4 resulted in elimination of CD4 T cells. Thus, it appears that macrophages play a role in anti-CD4-induced T cell elimination. While anti-CD4 did not eliminate CD4 cells from a population of purified T cells, there was profound down-regulation of cell surface CD4. Activating T cells with immobilized anti-CD3 before addition of anti-CD4 prevented down-regulation of CD4. These experiments demonstrate that T cell activation by anti-CD3 renders the activated cells resistant to antibody-induced CD4 down-regulation and to antibody-induced CD4 T cell depletion. These findings may have relevance to the application of anti-CD4 therapy in human diseases that are mediated by activated Th cells.
Details
- Title: Subtitle
- Kinetics of anti-CD4-induced T helper cell depletion and inhibition of function. Activation of T cells by the CD3 pathway inhibits anti-CD4-mediated T cell elimination and down-regulation of cell surface CD4
- Creators
- Iyad Jamali - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242Elizabeth H FieldAudrey FlemingJohn S Cowdery
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.148(6), pp.1613-1619
- DOI
- 10.4049/jimmunol.148.6.1613
- PMID
- 1347302
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- DK42418 / NIDDK NIH HHS
- Language
- English
- Date published
- 03/15/1992
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094621302771
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