Table 1.
Summary of known CD4 cytotoxic T lymphocyte (CTL) phenotype and mechanism of cytolysis in human, non-human primate (NHP), and murine models.
| Model | Phenotype | Conditions | Reference | |
|---|---|---|---|---|
| Healthy adults | Cell surface | CD11a/b+, CD27−, CD28− CD45RO+, CCR7− | Appay et al. (9) | |
| Activation | CD38lo, CD69−, Bcl2++, Ki67− | Appay (56) | ||
| Differentiation | CD57+, perforin, GzmB | Appay et al. (9) and Appay (56) | ||
| Effector | CD57+, FRCL6+, NKG2D+, perforin+ | Schreeder et al. (57) | ||
| Senescence | NKG2D+ | Alonso-Arias et al. (58) | ||
| Regulatory T cells (Tregs) | Human | GzmB+ | In vitro (αCD3, αCD28, IL-2) | Efimova and Kelley (106) |
| Tregs | Murine | GzmA+, GzmB+, perforin+ | In vitro phenotype (effector CD4 T-cell+ IL-2++) | Czystowska et al. (111) |
| Infection/pathogen | ||||
| Human immunodeficiency virus type 1 (HIV-1) | Human | GzmA+, perforin+, TIA-1/GMP-17+ | Appay et al. (9) | |
| Acute HIV-1 | Human | CD38+++, CD57−, Bcl2lo, IFN-γ, Ki67+, TIA-1+ | Zaunders et al. (117) | |
| Simian immunodeficiency virus | NHP | CD28+, CD45RA−, CD95+, CCR7−, GrzmB+ | von Gegerfelt et al. (113) | |
| Cytomegalovirus (CMV) | Human | CD28−, CD27−, GzmB+, perforin+ | Therapy cessation | van Leeuwen et al. (12) |
| CD27−, CD28−, perforin+ | Latent CMV | Appay et al. (9) | ||
| CD244+, CCR5+, GzmA+ IFN-γ+, TIA-1+ | Latent CMV | Zaunders et al. (10) and Zaunders et al. (117) | ||
| CD107a, GzmA+ GzmB+, IFN-γ+, MIP-1β+, perforin+, TNF+ | Latent CMV | Casazza et al. (21) | ||
| CX3CR1+, Gransulysin+, GzmA/B/H+, IFN-γ+, perforin+, TNF+ | In vitro phenotype | Pachnio et al. (130) | ||
| CD28−, CX3CR1+, NKG2D+, perforin+ | Posttransplant | Shabir et al. (132) | ||
| Acute CMV | Human | CD27−, CD28+, IFN-γ+, GrzmB+, TNF+ (acute) | Gamadia et al. (128) | |
| Epstein–Barr virus | Human | Eomes+Tbet+ | In vitro phenotype (CD137) | Akhmetzyanova et al. (151) |
| Influenza | Human | Perforin+, GzmB+ | Vaccine phenotype (BMDC, αCD3, IFN-γ, IL-2), in vitro phenotype | Zhou and McElhaney (126) |
| Influenza | Mouse | GzmB+ | (CpG stimulus) | Vogel and Brown (164) |
| GzmB+ | (PR8) | Brown et al. (72) | ||
| Perforin+, GzmB+ | In vitro phenotype and tissue resident | Hua et al. (64) | ||
| Vaccinia | Human | CD4+ CD8− Leu11− | Littaua et al. (159) | |
| Demkowicz et al. (160) | ||||
| IFN-γ+ TIA-1+ CD57− | Vaccine phenotype | Zaunders et al. (14) | ||
| GrzmA, GrzmK, KLRB1/CD161, Rab27a, granulysin, TIA-1, perforin | Microarray analysis | Munier et al. (15) | ||
| Ectromelia | Mouse | GzmB+ | Fang et al. (157) | |
| Hepatitis | Human | Perforin+ | Hepatitis B virus | Aslan et al. (28) |
| Perforin+ | Hepatitis C virus | Aslan et al. (28) | ||
| Perforin++ | Hepatitis D virus | Aslan et al. (28) | ||
| Dengue | Human | Perforin+ | Antigen-presenting cell targets | Gagnon et al. (77) |
| Fas/FasL | HepG2 cells | Weiskopf et al. (155) | ||
| CD45RA+ CCR6−, CCR7−, CCR4−, CXCR3−, CD8a+, CD107a+, Gzm+, Eomes+, CX3CR1+ | ||||
| Parvovirus | Human | CD57+, GzmB+, perforin+, IL-17+ | In vitro phenotype | Kumar et al. (34) |
| Hantavirus | Human | GzmB+, perforin+, CD107a± | Ma et al. (29) | |
| Human papillomavirus | Human | CD28− NKG2D+ (CD107a and CD161 negatively correlated with frequency) | Garcia-Chagollan et al. (102) | |
Parentheses () indicate the conditions applied to each model, which has been linked to phenotype.