Written and maintained by CASRAI Editorial Board
Last updated
Short answer: memory T cells are antigen-experienced T cells that persist after an immune response and respond faster on re-encounter. In humans they are usually separated into central memory (TCM, CD45RA-CCR7+), effector memory (TEM, CD45RA-CCR7-) and tissue-resident memory (TRM, non-circulating, CD69+) populations, with stem cell-like memory (TSCM) and TEMRA cells as further CD45RA+ groups.
This page is for researchers and lab staff who need to name a memory subset, read a flow-cytometry gating scheme, or decide what a blood sample can and cannot show. It is general scientific information, not clinical or individual medical advice.
Definition and scope
Memory T cells are the long-lived product of T cell activation. The classical human definition is CD45RO-positive and CD45RA-negative, but Farber, Yudanin and Restifo describe the pool as heterogeneous: it divides into subsets that differ in where they live, how far they circulate, how readily they proliferate and which cytokines they make. Memory T cells are the most abundant T cell subset in mucosal sites, skin, spleen and bone marrow (Farber et al., 2014). Thome and Farber add that cells with a tissue-resident memory phenotype make up the majority of T cells throughout the body (Thome and Farber, 2015). For the isoform background behind the CD45RO and CD45RA labels, see the CD45 guide; for the wider field, see what is immunology.
How memory T cells are identified in practice
Subsets are defined by combinations of surface markers rather than any single one. The two sources read for this page use these markers:
- CD45RA and CD45RO separate naive-like from antigen-experienced cells; memory is classically CD45RO+CD45RA-.
- CCR7 splits the CD45RA-negative cells into central memory (CCR7+) and effector memory (CCR7-).
- CD69 is expressed by tissue-resident memory cells across human tissues, and CD103 is largely confined to CD8 memory T cells in mucosal sites and skin. Blood T cells are CD69- and CD103- (Thome and Farber, 2015).
- CD27, CD28, IL-7Rα and CD62L are high on stem cell-like memory cells (Farber et al., 2014).
A multicolour panel built for this purpose depends on a stable instrument; see multicolour flow cytometry instrument setup and QC beads.
Memory T cell subsets compared
| Subset | Defining markers | Where found / behaviour | Functional profile | Source |
|---|---|---|---|---|
| TCM (central memory) | CD45RA-, CCR7+ | Traffics to lymphoid tissue | More IL-2; higher proliferative capacity | Farber et al., 2014 |
| TEM (effector memory) | CD45RA-, CCR7- | Migrates to multiple peripheral tissues | More effector cytokines; highest proportion of IFN-γ and TNF producers | Farber et al., 2014 |
| TSCM (stem cell-like memory) | CD45RA+, CD45RO-; high CD27, CD28, IL-7Rα, CD62L, CCR7 | Described as stem cell-like | High proliferative capacity; self-renewing and multipotent | Farber et al., 2014 |
| TRM (tissue-resident memory) | CD69+; CD8+ cells also CD103+; CD4+ TRM are CCR7- | Non-circulating; persist in tissues; most abundant in lungs, intestines, skin and bone marrow | Polyfunctional; rapid protection in situ | Farber et al., 2014; Thome and Farber, 2015 |
| TEMRA | CD45RA+, CCR7- (CD8+) | Circulating; absent from mucosal sites, skin and lymph nodes; accumulate with age | Rapid effector function; a major subset specific for CMV | Thome and Farber, 2015 |
Where it matters for labs: blood versus tissue
The practical consequence of the table is a sampling limit. Thome and Farber report that blood sampling will not capture long-lived memory such as TRM, and that assessing protective T cell responses to vaccines requires looking at tissues; for example, the human lung is enriched in influenza-specific T cells compared with blood or spleen. A peripheral-blood panel therefore describes circulating subsets (TCM, TEM, TEMRA, TSCM) and cannot stand in for tissue memory. Skin TRM were also reported to persist after alemtuzumab depletion.
Gating checklist derived from the table
- Gate T cells, then CD4+ or CD8+.
- Split on CD45RA and CCR7: CD45RA-CCR7+ is TCM, CD45RA-CCR7- is TEM, CD45RA+CCR7- (CD8+) is TEMRA.
- TSCM are CD45RA+CD45RO- with high CD27, CD28, IL-7Rα, CD62L and CCR7, so they need those additional markers rather than a CD45RA and CCR7 gate alone.
- For tissue samples, add CD69 (and CD103 for CD8+ cells) to identify TRM.
Common misunderstandings
- “Memory means CD45RO+ only.” The classical definition is CD45RO+CD45RA-, but TSCM and TEMRA are CD45RA+ subsets described in the memory literature.
- “Blood memory cells represent the whole body.” Blood T cells are CD69-/CD103- and miss non-circulating TRM.
- “Effector memory and TEMRA are the same.” Both lack CCR7, but TEMRA are CD45RA+ and, per Thome and Farber, are absent from mucosal sites, skin and lymph nodes.
FAQ
What are memory T cells?
Antigen-experienced T cells that persist after an immune response; in humans they are classically CD45RO+CD45RA- and form a heterogeneous group of subsets (Farber et al., 2014).
What is the difference between TCM and TEM?
Both are CD45RA-. TCM express CCR7, traffic to lymphoid tissue and make more IL-2 with higher proliferative capacity; TEM lack CCR7, migrate to peripheral tissues and include the highest proportion of IFN-γ and TNF producers.
What are tissue-resident memory T cells?
Non-circulating memory cells that persist in tissues, express CD69 and, for CD8+ cells, CD103; they are most abundant in lungs, intestines, skin and bone marrow.
Can a blood sample show tissue memory?
No. Blood sampling will not capture long-lived tissue memory such as TRM (Thome and Farber, 2015).
Sources
- Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nature Reviews Immunology, 2014. pmc.ncbi.nlm.nih.gov/articles/PMC4032067 (read 2026-11-08).
- Thome JJC, Farber DL. Emerging concepts in tissue-resident T cells: lessons from humans. Trends in Immunology, 2015;36(7):428-435. pmc.ncbi.nlm.nih.gov/articles/PMC4491028 (read 2026-11-08).
