Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function

作者：Gorman Jacob V; Colgan John D^*

来源：Immunology, 2018, 154(3): 418-433.

DOI：10.1111/imm.12890

• CD4 cell
• cytokines
• inhibitory
• activating receptors
• T helper type 1
• viral

T-cell immunoglobulin and mucin domain 3 (Tim-3) is a surface receptor expressed by T helper type 1 (Th1) effector CD4 T cells, which are critical for defence against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed that Tim-3 expression makes Th1 cells more susceptible to apoptosis and also marks functionally impaired T cells that arise due to chronic stimulation. However, other studies suggested that Tim-3-expressing Th1 cells do not always have these properties. To further define the relationship between Tim-3 and Th1 cell function, we analysed the characteristics of Th1 cells that expressed Tim-3 in response to brief stimulation in vitro or an acute viral infection in vivo. As expected, cultured CD4 T cells began expressing Tim-3 during Th1 differentiation and secondary stimulation generated Tim-3(-) and Tim-3(+) fractions that were separated and further analysed. When injected into naive mice, Tim-3(+) cells down-regulated Tim-3 and survived equally well compared with Tim-3(-) cells. Further, Tim-3(-) and Tim-3(+) Th1 cells had similar functional responses when transferred into naive mice that were subsequently infected with lymphocytic choriomeningitis virus (LCMV). Cultured Th1 cells that expressed Tim-3 following T-cell receptor stimulation had a greater capacity to express signature Th1 cytokines than their Tim-3(-) counterparts and showed differential expression of genes that regulate CD4 T-cell function. Consistent with these findings, Tim-3(+) Th1 cells generated in response to LCMV infection displayed augmented effector function relative to Tim-3(-) cells. These results suggest that Tim-3 expression by Th1 cells responding to acute stimulation can mark cells that are functionally competent and have an augmented ability to produce cytokines.

• 出版日期2018-7