Abstract
Regulation of homeostasis in the immune system includes mechanisms that promote survival of resting T lymphocytes, and others that control activation-induced cell death (AICD). In this study, we report on the use of a transgenic mouse model to test the role of CD4-MHC class H interactions for the susceptibility of CD4+ T lymphocytes to AICD, and for the survival of resting CD4+ T cells in peripheral lymphoid organs. The only I-A(β) gene expressed in these mice is an A(β)(k) transgene with a mutation that prevents MHC class H molecules from interacting with CD4. We show increased apoptosis in CD4+ T lymphocytes derived from wild-type, but not from mutant A(β)(k) transgenic mice following stimulation with staphylococcal enterotoxin A. Therefore, AICD may be impaired in CD4+ T cells derived from mutant A(β)(k) transgenic mice. Importantly, we observed much higher apoptosis in resting CD4+ T cells from mutant A(β)(k) transgenic mice than from wild-type mice. Furthermore, resting CD4+ T cells from mutant A(β)(k) transgenic mice expressed higher levels of cell surface CD95 (Fas, APO-1). Ab-mediated cross-linking of CD95 further increased apoptosis in CD4+ T cells from mutant A(β)(k) transgenic mice, but not from wild-type mice, suggesting apoptosis involved CD95 signaling. When cocultured with APC- expressing wild-type MHC class H molecules, apoptosis in resting CD4+ T lymphocytes from mutant A(β)(k) transgenic mice was reduced. Our results show for the first time that interactions between CD4 and MHC class H molecules are required for the survival of resting CD4+ T cells in peripheral lymphoid organs.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5973-5980 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 162 |
| Issue number | 10 |
| State | Published - May 15 1999 |
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ASJC Scopus subject areas
- Immunology
Cite this
Requirement for efficient interactions between CD4 and MHC class II molecules for survival of resting CD4+ T lymphocytes in vivo and for activation-induced cell death. / Maroto, Rosario; Shen, Xiaoli; König, Rolf.
In: Journal of Immunology, Vol. 162, No. 10, 15.05.1999, p. 5973-5980.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Requirement for efficient interactions between CD4 and MHC class II molecules for survival of resting CD4+ T lymphocytes in vivo and for activation-induced cell death
AU - Maroto, Rosario
AU - Shen, Xiaoli
AU - König, Rolf
PY - 1999/5/15
Y1 - 1999/5/15
N2 - Regulation of homeostasis in the immune system includes mechanisms that promote survival of resting T lymphocytes, and others that control activation-induced cell death (AICD). In this study, we report on the use of a transgenic mouse model to test the role of CD4-MHC class H interactions for the susceptibility of CD4+ T lymphocytes to AICD, and for the survival of resting CD4+ T cells in peripheral lymphoid organs. The only I-A(β) gene expressed in these mice is an A(β)(k) transgene with a mutation that prevents MHC class H molecules from interacting with CD4. We show increased apoptosis in CD4+ T lymphocytes derived from wild-type, but not from mutant A(β)(k) transgenic mice following stimulation with staphylococcal enterotoxin A. Therefore, AICD may be impaired in CD4+ T cells derived from mutant A(β)(k) transgenic mice. Importantly, we observed much higher apoptosis in resting CD4+ T cells from mutant A(β)(k) transgenic mice than from wild-type mice. Furthermore, resting CD4+ T cells from mutant A(β)(k) transgenic mice expressed higher levels of cell surface CD95 (Fas, APO-1). Ab-mediated cross-linking of CD95 further increased apoptosis in CD4+ T cells from mutant A(β)(k) transgenic mice, but not from wild-type mice, suggesting apoptosis involved CD95 signaling. When cocultured with APC- expressing wild-type MHC class H molecules, apoptosis in resting CD4+ T lymphocytes from mutant A(β)(k) transgenic mice was reduced. Our results show for the first time that interactions between CD4 and MHC class H molecules are required for the survival of resting CD4+ T cells in peripheral lymphoid organs.
AB - Regulation of homeostasis in the immune system includes mechanisms that promote survival of resting T lymphocytes, and others that control activation-induced cell death (AICD). In this study, we report on the use of a transgenic mouse model to test the role of CD4-MHC class H interactions for the susceptibility of CD4+ T lymphocytes to AICD, and for the survival of resting CD4+ T cells in peripheral lymphoid organs. The only I-A(β) gene expressed in these mice is an A(β)(k) transgene with a mutation that prevents MHC class H molecules from interacting with CD4. We show increased apoptosis in CD4+ T lymphocytes derived from wild-type, but not from mutant A(β)(k) transgenic mice following stimulation with staphylococcal enterotoxin A. Therefore, AICD may be impaired in CD4+ T cells derived from mutant A(β)(k) transgenic mice. Importantly, we observed much higher apoptosis in resting CD4+ T cells from mutant A(β)(k) transgenic mice than from wild-type mice. Furthermore, resting CD4+ T cells from mutant A(β)(k) transgenic mice expressed higher levels of cell surface CD95 (Fas, APO-1). Ab-mediated cross-linking of CD95 further increased apoptosis in CD4+ T cells from mutant A(β)(k) transgenic mice, but not from wild-type mice, suggesting apoptosis involved CD95 signaling. When cocultured with APC- expressing wild-type MHC class H molecules, apoptosis in resting CD4+ T lymphocytes from mutant A(β)(k) transgenic mice was reduced. Our results show for the first time that interactions between CD4 and MHC class H molecules are required for the survival of resting CD4+ T cells in peripheral lymphoid organs.
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M3 - Article
VL - 162
SP - 5973
EP - 5980
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -