ICOS is required for the generation of both central and effector CD4(+) memory T-cell populations following acute...

Area of Science:

• Immunology
• T-cell biology
• Immune memory

Background:

• Inducible T-cell costimulator (ICOS) and its ligand (ICOSL) interactions are vital for T follicular helper (Tfh) cell development and germinal center (GC) reactions.
• Conflicting reports exist regarding the necessity of ICOS signals for other CD4(+) T-cell populations.

Purpose of the Study:

• To investigate the specific roles of ICOS signaling in CD4(+) T-cell responses in vivo.
• To compare the requirements for ICOS signaling with those for CD28 signaling during primary and secondary immune responses.

Main Methods:

• Utilized in vivo approaches in mice to study endogenous CD4(+) T-cell responses.
• Employed genetic absence of ICOSL and blocking antibodies against ICOS (anti-ICOS mAb).
• Contrasted ICOS signaling requirements with CD28 signaling blockade using CTLA4Ig.

Main Results:

• Absence of ICOSL or ICOS blockade led to a modest reduction in total CD4(+) T cells but a severe decrease in T central memory and T effector memory cells.
• ICOS blockade had a more substantial impact than CD28 blockade on memory cell formation during the primary response.
• While ICOS and CD28 were not required for memory cell survival, ICOS remained essential for Tfh cell expansion upon secondary challenge, whereas CD28 was needed for optimal expansion of all subsets.

Conclusions:

• ICOS signaling is critically important for the formation of memory CD4(+) T cells.
• ICOS plays a specific role in Tfh cell expansion during secondary immune responses.
• Targeting the ICOS pathway presents a potential therapeutic strategy for modulating immune responses.