Abstract

Size and composition of γδ T cell populations change dramatically with tissue location, during development, and in disease. Given the functional differentiation of γδ T cell subsets, such shifts might alter the impact of γδ T cells on the immune system. To test this concept, and to determine if γδ 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 γδ 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 αβ T cells. Similarly to the B cells, αβ T cells evidently experience the influence of γδ T cells at late stages of their pre-immune differentiation, as single-positive heat stable antigen-low thymocytes. Changes in these and in mature αβ 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 αβ T cells were dependent on IL-4. Unexpectedly, IL-4 seemed to be produced mainly by αβ T cells in the non-immunized mice, albeit strongly regulated by γδ T cells. Similarly to our findings with B cells, changes of αβ T cells were less pronounced in mice lacking all γδ T cells than in mice lacking only some, suggesting that the composition of the γδ T cell population determines the nature of the γδ-influence on the other pre-immune lymphocytes.

Highlights

  • Introduction γδT cell populations change in numbers and in cellular composition with human age [1], and with infectious and autoimmune diseases [2]

  • To our findings with B cells, changes of αβ T cells were less pronounced in mice lacking all γδ T cells than in mice lacking only some, suggesting that the composition of the γδ T cell population determines the nature of the γδ-influence on the other pre-immune lymphocytes

  • We initially focused our investigation on the secondary changes in B cells, and confirmed that they were the result of interactions with the altered γδ T cell populations [18, 23]

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Summary

Introduction

Introduction γδT cell populations change in numbers and in cellular composition with human age [1], and with infectious and autoimmune diseases [2]. June 25, 2019 γδ T cells shape αβ T cell populations incompletely restored [3, 4]. Mouse ontogeny is associated with an ordered appearance of γδ T cells expressing different TCR-Vγ genes (subsets), causing compositional shifts in the population over time. Throughout life, different mouse tissues contain γδ T cell populations with distinct subset compositions [5, 6]. It was found that the TCR-Vγ-defined cell subsets have different functional potentials [7,8,9,10,11,12], suggesting a connection between innate TCR-ligand-specificities and functional differentiation [13,14,15], and overall changes of γδ T cell functions during ontogeny and between the tissues

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