What is GARP?
GARP (glycoprotein A repetitions predominant, LRRC32, Garpin) is a recent addition to the growing collection of proteins expressed by regulatory T cells (Treg).
What makes GARP unique?
- GARP is only expressed on activated Treg.
- GARP is not expressed on unactivated/quiescent Treg.
- Unlike markers such as CD25, GITR/AITR, and CTLA-4, GARP is not expressed on activated conventional T cells.
Additionally, in human cells, Foxp3 itself is transiently upregulated in conventional T cells following activation, making GARP one of the only unique markers for Treg in activated samples (Figure 1).
Figure 1. GARP is expressed on activated Treg and not on unactivated Treg or on activated conventional CD4+ T cells.
Normal human peripheral blood cells were cultured alone (top row) or were activated with plate-bound anti-CD3, soluble anti-CD28, and recombinant human IL-2 for 24 hours (middle & bottom row). The cells were stained for CD4, CD25, Foxp3, and GARP (top & middle row) or isotype control (bottom row). Viable CD4+ cells were used for analysis.
What is GARP's role in Treg Biology?
The role that GARP plays in Treg biology is still somewhat unclear. However, several groups have shown that GARP presents latent TGFβ (LAP/TGFβ) on the cell surface, and thus GARP and LAP are co-expressed on the surface of activated Treg (Figure 2). It is thought that the presentation of LAP/TGFβ on the surface of Treg is at least part of the mechanism used by Treg to suppress immune responses in a cell-contact/cell-proximity-dependent manner.
Figure 2. GARP and LAP are co-expressed on activated Treg.
Normal human peripheral blood cells were cultured alone (left) or were activated with plate-bound anti-CD3, soluble anti-CD28, and recombinant human IL-2 for 24 hours (right). The cells were stained for CD4, Foxp3, GARP, and LAP. Viable lymphocytes (top row) and CD4+Foxp3+ cells (bottom row) were used for analysis.