Table 1.
Role of CD4 T cells in herpes viral infections.
| Viral infection | Role of CD4 T cells |
|||
|---|---|---|---|---|
| Establishment of viral latency/control of lytic viral replication | Maintenance of latency/inhibition of viral recrudescence | Immunopathology/immune senescence | Protective role in immunotherapy or immunization | |
| HSV | Primary immunodeficiency (Carneiro-Sampaio and Coutinho, 2007); vaginal tract, sensory ganglia in mice (Milligan and Bernstein, 1997; Gill and Ashkar, 2009) | Immunopathology (Hendricks and Tumpey, 1990; Hendricks et al., 1992) | Protective role in vaccine models (Milligan et al., 1998; BenMohamed et al., 2003); major mediator of immunity in cornea (Hendricks and Tumpey, 1990; Hendricks et al., 1992) | |
| VZV | Primary immunodeficiency (Carneiro-Sampaio and Coutinho, 2007); inverse correlation between viremia and virus-specific CD4 T cell response (Abendroth and Arvin, 2001; Malavige et al., 2008); SVV: (VZV infection model in rhesus macaques) prolonged viremia and higher viral titers in CD4 T cell depleted animals (Haberthur et al., 2011) | Positive correlation between CD4 T cell immunity and protection in the aged (Levin and Hayward, 1996; Weinberg et al., 2009) and in hematopoietic cell transplant recipients (Hata et al., 2002); increased reactivation in HIV carriers (Buchbinder et al., 1992) | Tonsillar CD4 T cells carry virus from the LN to the skin (Ku et al., 2002, 2004) | Protective role in transplant recipients with antiviral adoptive transfer treatment (Hata et al., 2002; Blyth et al., 2012) |
| MCMV | Particularly at mucosal sites (salivary glands) (Jonjic et al., 1989, 1990; Walton et al., 2011a) | Polic et al. (1998) | CD4 T cells isolated from CD8 deficient mice (Jonjic et al., 1990) | |
| HCMV | Primary immunodeficiency (Carneiro-Sampaio and Coutinho, 2007); inverse correlation between viremia and virus-specific CD4 T cell response (young children versus adults) (Tu et al., 2004) | Reactivation in HIV patients with low CD4 T cell counts (Gallant et al., 1992; Cinque et al., 1998); loss of CMV-specific CD4 T cells (Komanduri et al., 1998, 2001b) | Graft-versus-host disease (Cray and Levy, 1993); myocarditis (Lenzo et al., 2002), atherosclerosis (Sacre et al., 2012), immune senescence (Karrer et al., 2009) | Transplant recipients (Einsele et al., 2002; Gamadia et al., 2003, 2004; Tormo et al., 2011; Akulian et al., 2013), septic shock patients (von Muller et al., 2007) |
| MHV-68 | Particularly at mucosal sites (lung) (Christensen et al., 1999; Sparks-Thissen et al., 2005) | Cardin et al. (1996) | Adoptive transfer (Sparks-Thissen et al., 2005); immunization (Liu et al., 1999) | |
| EBV | Primary immunodeficiency (Carneiro-Sampaio and Coutinho, 2007) | Reactivation in immunosuppressed patients with low CD4 T cell counts (Sebelin-Wulf et al., 2007) | Implicated in sustaining primary infection (Veronese et al., 1992; Fu and Cannon, 2000; Johannessen et al., 2000; Wagar et al., 2000; MacArthur et al., 2007) | Protective role in PTLD disorders following adoptive transfer of virus-specific CD4 T cells (Haque et al., 2007); murine model of PTLD-like and Burkitt’s lymphoma (Fu et al., 2004; Merlo et al., 2010) |