effector T cell

**Generation (priming in secondary lymphoid organs):** - Naive T cells recirculate through lymph nodes (enter via HEV using L-selectin/CD62L and CCR7). A dendritic cell presents antigen. - Signal 1: TCR + CD3 binds peptide-MHC (CD4 binds MHC II; CD8 binds MHC I). - Signal 2 (costimulation): B7 (CD80/86) on APC binds CD28 on T cell. Signal 1 without signal 2 causes anergy. - Signal 3: cytokines direct differentiation. - IL-2 drives clonal expansion (autocrine). CTLA-4 (binds B7) and PD-1 (binds PD-L1) are inhibitory checkpoints; checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) enhance effector T cell function against tumors.

**CD8+ cytotoxic T lymphocytes (CTLs):** - Recognize endogenous antigens (viral, tumor) on MHC I, and kill infected cells, tumor cells, and allograft cells. - Mechanisms: perforin and granzymes (induce apoptosis through caspases), Fas ligand-Fas (death receptor pathway), and IFN-γ/TNF-α release. - Cross-presentation by dendritic cells primes naive CD8 cells.

**CD4+ effector (helper) T cells (all MHC II-restricted):** - Th1: induced by IL-12 (from macrophages/DCs) and IFN-γ. Master regulator T-bet. Secretes IFN-γ, which activates macrophages and promotes class switching to opsonizing IgG. Defends against intracellular pathogens (e.g., mycobacteria, granuloma formation). Involved in type IV hypersensitivity (delayed-type). Defects in IL-12/IFN-γ axis cause disseminated mycobacterial disease. - Th2: induced by IL-4. Master regulator GATA-3. Secretes IL-4 (IgE and IgG switching), IL-5 (eosinophils, IgA), and IL-13. Defends against helminths and is involved in type I hypersensitivity (allergy, asthma). - Th17: induced by TGF-β + IL-6 (and IL-23 for maintenance). Master regulator RORγt. Secretes IL-17, IL-21, and IL-22. Recruits neutrophils and defends against extracellular bacteria and fungi. Defects (e.g., hyper-IgE/Job syndrome, STAT3 mutation; chronic mucocutaneous candidiasis) cause impaired defense. Implicated in autoimmunity (psoriasis, IBD, ankylosing spondylitis). - Tfh (follicular helper): IL-21, CD40L; help B cells in germinal centers with class switching and affinity maturation. Defect in CD40L causes hyper-IgM syndrome. - Regulatory T cells (Treg, CD4+CD25+FoxP3+) are sometimes grouped separately: they suppress immunity via IL-10, TGF-β, and IL-2 consumption. FOXP3 mutation causes IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked). - Cross-regulation: IFN-γ inhibits Th2; IL-4 and IL-10 inhibit Th1.

**Clinical significance:** - HIV: gp120 binds CD4 and CCR5/CXCR4, which depletes CD4+ effector and memory T cells and leads to opportunistic infections (CD4 <200). - Transplant: acute cellular rejection is mediated by CD8+ and CD4+ effector T cells (weeks to months); immunosuppressants like cyclosporine/tacrolimus block calcineurin/NFAT and reduce IL-2 transcription. Basiliximab blocks CD25 (IL-2 receptor). - Type IV hypersensitivity: contact dermatitis (Th1/CD8), PPD (tuberculin) test, and graft-versus-host disease. - Autoimmunity: T1DM (CD8 destruction of β cells), multiple sclerosis (Th1/Th17), and RA. - Thymic DiGeorge syndrome (22q11.2 deletion): low T cell number and function. - SCID: absent T cell function.

**Fate after the response:** - Most effector cells die by activation-induced cell death (Fas-FasL) after antigen clearance (contraction phase). - A minority persist as memory T cells: central memory (CCR7+, lymph node homing) and effector memory (CCR7−, tissue-homing).

**Markers/Identification:** - CD3+ plus CD4 or CD8. Activated effector cells upregulate CD25 (IL-2Rα), CD69, CD40L (CD154), and HLA-DR, and downregulate L-selectin/CCR7 (to leave nodes and migrate to inflamed tissue through integrins such as LFA-1 and VLA-4).