memory T cell

**Origin and formation** - A naive T cell (CD45RA+, CCR7+, CD62L+) is activated in secondary lymphoid organs. It needs signal 1 (TCR binding peptide-MHC), signal 2 (costimulation, e.g., CD28 on the T cell binding B7 on the APC), and cytokines (signal 3). - The activated cell clonally expands and differentiates into effector cells. CD4+ cells become Th1, Th2, Th17, Tfh, or Treg. CD8+ cells become cytotoxic T lymphocytes. - After the antigen is cleared, most effector cells (~90–95%) die by apoptosis (contraction phase). A minority survive as memory T cells.

**Maintenance** - Memory cells survive without antigen. They are maintained by homeostatic cytokines, mainly IL-7 and IL-15 (IL-15 is especially important for CD8+ memory cells). - Memory cells have a lower activation threshold. They need less costimulation and respond faster than naive cells.

**Subsets** - **Central memory (T_CM):** CCR7+, CD62L+. They home to lymph nodes, proliferate robustly on re-challenge, and have limited immediate effector function. - **Effector memory (T_EM):** CCR7-, CD62L-. They circulate through peripheral tissues and show rapid effector function (e.g., IFN-γ production, cytotoxicity). - **Tissue-resident memory (T_RM):** CD69+, CD103+. They stay in barrier tissues (skin, lung, gut) and give frontline protection.

**Markers** - Memory T cells express CD45RO, produced by alternative splicing of CD45. Naive cells express CD45RA. - Memory cells also express high levels of CD44.

**Clinical significance** - **Vaccination:** Generating memory T and B cells is the goal of vaccination. Live attenuated vaccines generate strong cell-mediated memory, including CD8+ responses. - **Secondary immune response:** The response is faster and stronger than the primary one. - **Type IV hypersensitivity:** The tuberculin (PPD) skin test depends on memory CD4+ Th1 cells. They recognize mycobacterial antigens, release IFN-γ, and recruit macrophages, producing induration at 48–72 h. A positive test shows prior sensitization, not necessarily active disease. Contact dermatitis (e.g., poison ivy, nickel) also involves memory T cells. - **HIV:** Memory CD4+ T cells (CCR5+) are the main targets and are depleted early, especially in gut-associated lymphoid tissue. Latently infected resting memory CD4+ cells form the viral reservoir that prevents cure. - **Transplant and autoimmunity:** Memory T cells are less dependent on costimulation, so they are more resistant to costimulation blockade (e.g., belatacept). They contribute to rejection and to relapses in autoimmune disease. - **Immunodeficiency:** Defects in T-cell function (e.g., DiGeorge syndrome, SCID) impair memory responses and increase susceptibility to opportunistic infection. - **Cancer immunotherapy:** CAR-T cell persistence and the durability of checkpoint inhibitor responses depend on memory-like T cells.

**High-yield comparisons** - **Memory T vs. naive T:** Memory cells have a lower activation threshold, are CD45RO+ rather than CD45RA+, and have faster, stronger responses. - **Memory B cells:** These are the humoral counterpart. They undergo class switching and affinity maturation in germinal centers (a T-dependent process), then produce high-affinity IgG, IgA, or IgE on re-exposure. - **Boards pearl:** Polysaccharide capsule vaccines (e.g., unconjugated pneumococcal vaccine) are T-independent and poorly generate memory. Conjugating them to a protein carrier recruits T-cell help and produces memory.