Abstract
The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal trensduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) α chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.
| Original language | English |
|---|---|
| Pages (from-to) | 1807-1816 |
| Number of pages | 10 |
| Journal | Journal of Clinical Investigation |
| Volume | 89 |
| Issue number | 6 |
| State | Published - Dec 1 1992 |
| Externally published | Yes |
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Keywords
- Cytokine receptor regulation
- Human immunodeficiency virus glycoprotein 120 receptor
- Lymphoproliferation
- Signal transduction
- T cell activation
ASJC Scopus subject areas
- Medicine(all)
Cite this
Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class ii major histocompatibility complex-restricted antigen-specific T helper clones T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals. / Oyaizu, Naoki; Chirmule, Narendra; Pahwa, Savita G.
In: Journal of Clinical Investigation, Vol. 89, No. 6, 01.12.1992, p. 1807-1816.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class ii major histocompatibility complex-restricted antigen-specific T helper clones T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals
AU - Oyaizu, Naoki
AU - Chirmule, Narendra
AU - Pahwa, Savita G
PY - 1992/12/1
Y1 - 1992/12/1
N2 - The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal trensduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) α chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.
AB - The CD4 molecule plays an essential role in antigen-induced activation of T helper (Th) cells, but its contribution to signal trensduction events resulting in physiologic T cell function is ill defined. By utilizing anti-CD4 monoclonal antibodies (MAbs) that recognize distinct epitopes of CD4, we have investigated the role of CD4 molecule in antigen-induced interleukin 2 (IL-2) and IL-2 receptor (IL-2R) α chain expression in class II major histocompatibility complex-restricted antigen-specific human Th clones. Pretreatment of the Th clones with Leu3a resulted in a dose-dependent suppression of antigen-induced proliferative responses, inositol phosphate accumulation, increase in free cytoplasmic calcium ions ([Ca2+]i), IL-2 mRNA accumulation, IL-2 secretion, and membrane IL-2R expression. IL-2R mRNA accumulation, however, was unaffected even at highest Leu3a concentrations. Leu3a treatment did not affect bypass activation of T cells with PMA plus ionomycin or activation via CD2 molecule. The MAb OKT4, which binds another domain of CD4, was not inhibitory. These results suggest that after T cell antigen receptor-CD3 activation, IL-2 gene induction, IL-2 secretion, and membrane IL-2R expression are absolutely dependent upon participation of CD4 molecules, phosphatidylinositol (PI) hydrolysis, and increase in [Ca2+]i. The requirement for IL-2R gene induction, however, occurs independently of CD4 molecule participation and PI hydrolysis.
KW - Cytokine receptor regulation
KW - Human immunodeficiency virus glycoprotein 120 receptor
KW - Lymphoproliferation
KW - Signal transduction
KW - T cell activation
UR - http://www.scopus.com/inward/record.url?scp=0026747810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026747810&partnerID=8YFLogxK
M3 - Article
VL - 89
SP - 1807
EP - 1816
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 6
ER -