γδ T cells shape memory-phenotype αβ T cell populations in non-immunized mice

Size and composition of gamma delta T cell populations change dramatically with tissue location, during development, and in disease. Given the functional differentiation of gamma delta T cell subsets, such shifts might alter the impact of gamma delta T cells on the immune system. To test this concept, and to determine if gamma delta T cells can affect other immune cells prior to an immune response, we examined non-immunized mice derived from strains with different genetically induced deficiencies in gamma delta T cells, for secondary changes in their immune system. We previously saw extensive changes in pre-immune antibodies and B cell populations. Here, we report effects on alpha beta T cells. Similarly to the B cells, alpha beta T cells evidently experience the influence of gamma delta T cells at late stages of their pre-immune differentiation, as single-positive heat stable anti-gen- low thymocytes. Changes in these and in mature alpha beta T cells were most prominent with memory-phenotype cells, including both CD8+ and CD4+ populations. As previously observed with B cells, most of the effects on alpha beta T cells were dependent on IL-4. Unexpectedly, IL-4 seemed to be produced mainly by alpha beta T cells in the non-immunized mice, albeit strongly regulated by gamma delta T cells. Similarly to our findings with B cells, changes of alpha beta T cells were less pronounced in mice lacking all gamma delta T cells than in mice lacking only some, suggesting that the composition of the gamma delta T cell population determines the nature of the gamma delta-influence on the other pre-immune lymphocytes.