Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8 ⁺ memory T cell subsets

Abstract

Several recent studies have demonstrated that T-helper cell-dependent events during the initial priming period are required for the generation of CD8 ؉ T cell-mediated protective immunity. The underlying mechanisms of this phenomenon have not yet been determined, mostly because of difficulties in studying memory T cells or their precursor populations at early stages during immune responses. We identified IL-7 receptor (CD127) surface expression as a marker for long-living memory T cells, most importantly allowing the distinction between memory and effector T cells early after in vivo priming. The combination of surface staining for CD127 and CD62L further separates between two functionally distinct memory cell subsets, which are similar (if not identical) to cell subsets recently described as central memory T cells (CD127 high and CD62L high ) and peripheral effector memory T cells (CD127 high and CD62L low ). Using this new tool of memory T cell analysis, we demonstrate that CD8 ؉ T cell priming in the absence of T cell help or CD40L specifically alters the generation of the effector memory T cell subset, which appears to be crucial for immediate memory responses and long-term maintenance of effective protective immunity. Our data reveal a unique strategy to obtain information about the quality of long-term protective immunity early during an immune response, a finding that may be applied in a variety of clinical settings, including the rapid monitoring of vaccination success.

CXCR5+ CCR7– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

“…In the model by Sallusto et al [11], CCR7 + CD62L + antigen-experienced CD8 T cells circulate through secondary lymphoid tissue and are termed central memory cells, while CCR7 -CD62L +/-effector memory CD8 T cells migrate to peripheral sites. However, the process of T cell differentiation in response to antigen is highly complex, and other cell surface receptors such as CD7, CD27, CD28, CD45RA, CCR5 and CD127 can be used to identify functionally distinct subsets of effector and memory T cells [12][13][14][15][16][17][18][19].…”

“…Most of these cells expressed CCR5, a chemokine receptor which enables homing to the inflammatory chemokines RANTES, MIP-1a and MIP1b [29]. A small proportion of the tonsil CXCR5 + CD8 T cells expressed the IL-7 receptor CD127, which, as data from murine models indicate, may be important for long-term memory T cell generation [15,16]. A majority of CXCR5 + CD8 T cells were CD57 -, but a clear subset with intermediate to high expression representing about a third of cells was also observed (Fig.…”

Defect of CD8+ Memory T Cells Developed in Absence of IL-12 Priming for Secondary Expansion

“…These are (i) a proliferation phase that involves the growth and differentiation of naïve CD8 + T cells into effector T cells; (ii) a contraction or transition phase that entails the transition from the large population of effector CD8 + T cells to a smaller population (≈ 5-10%) of long-lived CD8 + memory T (Tm) cells (2); and (iii) a maintenance phase that is comprised of long-term CD8 + Tm cell survival in the host. The long-lived CD8 + Tm cell population can be rapidly reactivated and expanded upon Ag restimulation for recall responses.…”

SOCS1 downregulation in dendritic cells promotes memory T-cell responses

“…Although studies using LCMV-infected mice have shown that these two molecules can mark CD8 + memory cell precursors [26][27][28]31], other studies using peptide-pulsed DCs or peptide immunization have shown that IL-7R is not a marker for such precursors [38][39][40][41]. Antigen-presenting cells expressing thymic leukemia antigen TL can boost CD8αα expression by T cells, and CD8αα expression induces IL-7Rα expression [29].…”

“…3B). Since IL-7R and CD8αα have been reported to be early markers of memory CD8 + T cells [26][27][28][29][30][31], IL-7R and CD8aa expression were tracked using flow cytometry on CD8 + T cells after the initial inoculation. No increases in CD8 + IL-7R + or CD8αα + cells were detected in blood or spleen in any of the mice we tested over the first 14 days after the second initial vaccination (data not shown).…”