CD49d Treg cells with high suppressive capacity are remarkably less efficient on activated CD45RA- than on naive CD45RA+ Teff cells.

BACKGROUND: Impairment of regulatory T cells (Tregs) in common autoimmune diseases seems likely. However, the extent of Treg deficiency (number, function) or differential susceptibility of T effector cells (Teffs) to suppression is not completely understood. We hypothesize that even in healthy individuals both cell populations are heterogeneous and differ in their suppressive capability and their susceptibility to suppression. MATERIAL AND METHODS: Lymphocytes were enriched by MACS for CD4(+)CD25(+) Tregs or CD4(+)CD25(-) Teffs. After multicolour staining (anti-CD25, anti-CD127, anti-CD49d or anti-CD45RA) highly purified Treg and Teff subpopulations were collected by FACS. Functional capacity of Tregs or suppressive susceptibility of Teffs was analyzed in an in vitro assay. RESULTS: When CD4(+)CD25(high)CD127(-/low) CD49d(-) Tregs were tested on naive CD4(+)CD127(+)CD25(-)CD45RA(+) Teffs (93.8 %) suppression was almost complete, while the suppressive capacity of CD4(+)CD25(high)CD127(-/low) CD49d(+) Tregs was significantly less (71.8 %). Suppressive activity was low when CD4(+)CD25(high)CD127(-/low) CD49d(+) Tregs were analyzed on CD4(+)CD127(+)CD25(-)CD45RA(-) Teffs (48.7%). CONCLUSION: Although CD49d(+) Tregs are functional, the suppressive capacity is significantly lower compared to CD49d(-) Tregs. CD45RA(+) Teffs can be completely suppressed, while CD45RA(-) Teffs display relative resistance. Phenotypic and functional heterogeneity of Tregs as well as Teffs has to be considered when analyzing deficiencies in immune regulation.