| First Author | Mao Y | Year | 2004 |
| Journal | Exp Hematol | Volume | 32 |
| Issue | 8 | Pages | 735-47 |
| PubMed ID | 15308325 | Mgi Jnum | J:91985 |
| Mgi Id | MGI:3051434 | Doi | 10.1016/j.exphem.2004.04.011 |
| Citation | Mao Y, et al. (2004) Overexpression of a mutant CTLA4 inhibits T-cell activation and homeostasis-driven expansion. Exp Hematol 32(8):735-47 |
| abstractText | OBJECTIVE: Interaction of B7 with CD28 and CTLA4 plays an important function in T-cell activation and homeostasis. Disruption of CD28, CTLA4, or both has shown impact on T-cell biology. This paper examined the consequences of overexpressing a tailless mutant form of CTLA4 on T-cell activation and in vivo expansion. MATERIALS AND METHODS: Retroviral gene transfer was used to infect bone marrow progenitor cells with either a control vector or a cytoplasmic domain-deleted mutant of CTLA-4 (DeltaCTLA4). The cells were subsequently adoptively transferred to RAG(-/-) mice and allowed to repopulate. The T cells derived from the reconstituted RAG(-/-) mice were analyzed functionally in vitro and in vivo. RESULTS: The T cells were defective in their ability for IL-2 secretion, survival, and proliferation in response to Ag/APC stimulation in vitro. Addition of exogenous IL-2 or normal T cells was able to rescue the survival defect and allow cell-cycle progression. In adoptive transfer studies, the naive T cells expressing DeltaCTLA4 exhibited compromised capability to expand in RAG(-/-) mice. Memory DeltaCTLA4T cells, however, were capable of proliferating in lymphopenic hosts to a similar extent as control memory T cells, but showed reduced survival. CONCLUSION: Surface DeltaCTLA4 has similar tolerogenic/regulatory activity as CTLA4-Ig. In contrast to CTLA4-Ig, the effect of DeltaCTLA-4 is autonomous. The inhibition of in vivo expansion by DeltaCTLA4 indicates developmental and/or activation stage dependency of costimulation in T cells. |
