Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Porcine gamma delta T cells have two levels of TCR gamma delta expression. Whereas TCR gamma delta(med) cells are mostly CD2(+)CD8(-) and CD2(+)CD8(+), TCR gamma delta(hi) cells are highly enriched for CD2(-)CD8(-). This distribution is independent of bacterial colonization and it is already established in the thymus prior to export of gamma delta cells to the periphery. Sorting and cultivation experiments revealed that CD2(-)CD8(-) gamma delta cells are unable to acquire CD2 and CD8, whereas CD2(+) subsets can gain or loose CD8. There is also differential susceptibility for proliferation between CD2(+) and CD2(-) gamma delta cells. Although CD2(-)CD8(-) almost do not proliferate, proliferation of CD2(+)CD8(-) and CD2(+)CD8(+) is substantial. Population of CD2(-) gamma delta cells is also absent in CD1(+) immature thymocytes. Additionally, subpopulations of CD2(+) and CD2(-) gamma delta cells in the thymus differ in expression of auxiliary surface molecules such as CD25, CD45RA/RC, and MHC class II. Moreover, TCR gamma delta(hi) cells can generate TCR gamma delta(med) cells but never the opposite. The only exception is the thymus, where a few TCR gamma delta(med) cells can be induced to TCR gamma delta(hi) but only under IL-2 influence. The repertoire of TCR delta is polyclonal in all subsets, indicating that there is the same extent of diversification and equal capability of immune responses. Results collectively indicate that CD2 expression determines two lineages of gamma delta cells that differ in many aspects. Because CD2(-) gamma delta cells are missing in the blood of humans and mice but are obvious in other members of gamma delta-high species such as ruminants and birds, our findings support the idea that circulating CD2(-) gamma delta T cells are a specific lineage. The Journal of Immunology, 2013, 190: 2111-2120.