Differentiation of Effector/Memory Vδ2 T Cells and Migratory Routes in Lymph Nodes or Inflammatory Sites

Abstract

Vδ2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and mount both immediate effector functions and memory responses after microbial infection. However, how Vδ2 T cells mediate different facets of a memory response remains unknown. Here, we show that the expression of CD45RA and CD27 antigens defines four subsets of human Vδ2 T cells with distinctive compartmentalization routes. Naive CD45RA+CD27+ and memory CD45RA−CD27+ cells express lymph node homing receptors, abound in lymph nodes, and lack immediate effector functions. Conversely, memory CD45RA−CD27− and terminally differentiated CD45RA+CD27− cells, which express receptors for homing to inflamed tissues, are poorly represented in the lymph nodes while abounding at sites of inflammation, and display immediate effector functions. These observations and additional in vitro experiments indicate a lineage differentiation pattern for human Vδ2 T cells that generates naive cells circulating in lymph nodes, effector/memory cells patrolling the blood, and terminally differentiated effector cells residing in inflamed tissues.

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

“…116 This phenotype represents cd T cells that have already tackled some hurdles in their life and have reduced proliferative capacity, but are still able to pull the trigger given their highly cytolytic potential. 117 Thus, differences in cd T cell numbers in relation to parameters such as gender and race that are inconsistent across the various populations studied 89,[113][114][115] may partly reflect the discrepant burdens that contribute to overall life stress experienced by members of these groups. For example, African Americans in Baltimore were found to have significantly lower peripheral blood cd T cells in comparison to their Caucasian counterparts; 113 however, Africans from Ghana have significantly more cd T cells (of both the Vd1 and Vd2 T cell variety) in comparison to Europeans.…”

Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vγ9Vδ2 naive, memory and effector T cell subsets

“…Naive (T naive ) CD45RA + CD27 + and central memory (T CM ) CD45RA -CD27 + cells express lymph node homing receptors, abound in lymph nodes and lack immediate effector functions. Conversely, effector memory (T EM ) CD45RA -CD27 -and terminally differentiated (T EMRA ) CD45RA + CD27 -cells express receptors for migration to inflamed tissues, are poorly represented in the lymph nodes while abounding at sites of inflammation, where they display immediate effector functions (cytokine production and cytotoxicity, respectively) [2].…”

“…A progressive and irreversible differentiation in vitro from T naive to T CM and T EM has been demonstrated for Vc9Vd2 T lymphocytes [2], but the relationship between the various subpopulations is still unclear. Moreover, little is known about the homeostasis of human Vc9Vd2 T lymphocytes and, in particular, how the functional heterogeneity of the memory pool is maintained.…”

“…Because T naive , T CM , T EM and T EMRA Vc9Vd2 T lymphocytes have different capacities to traffic in lymphoid and nonlymphoid tissues [2], it is possible that they have access to different environments and possibly to different survival stimuli, although the responsiveness of naive and memory Vc9Vd2 T cell subsets to cytokines has not been investigated. We therefore considered the possibility that the phenotype and function of distinct subsets of Vc9Vd2 T lymphocytes may be influenced by homeostatic mechanisms.…”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…119,120 Chemokines are another important group of soluble factors that determine the outcome of cd-T cell-mediated anti-infection immune responses. It has been found that RANTES, MIP1a/b and CXCL9/10/ 11 secreted from infected cells guide the migration of CCR5 26 -and CXCR3 136 -expressed IPP-activated Vc9Vd2 cd-T cells to influenzainfected sites and facilitate the elimination of pathogens.…”