Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

Abstract

The human NKG2D killer lectin‐like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3‐kinase (PI3 K) and specifically interacts with different stress‐inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus‐infected cells. This KLR is commonly expressed by human NK cells as well as TCRγδ+ and TCRαβ+CD8+ T lymphocytes, but it has been also detected in CD4+ T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)‐specific CD4+ T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4+NKG2D+ T lymphocytes that coexpressed perforin. NKG2D was detected in CD28– and CD28dull subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR‐dependent activation of CD4+ T cells, triggering proliferation and cytokine production (i.e. IFN‐γ and TNF‐α). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV‐specific CD4+ T lymphocytes and thus may have a role in the response against infected HLA class II+ cells displaying NKG2D ligands.

Relationship between functional ability in older people, immune system status, and intensity of response to CMV

“…Similarly, double-positive CD4+CD8+ T cells (Pawelec 1995), which generally contain a high proportion of memory and differentiated cells, were also increased in groups with worse functional status. CD4+NKG2D+ and CD4+CD8+ subsets have been associated with CMV infection; there was a significant correlation between their expansion and CMV infection and viral reactivation (Saez-Borderias et al 2006;Alonso-Arias et al 2009). …”

Functional Killer Ig-Like Receptors on Human Memory CD4+ T Cells Specific for Cytomegalovirus

“…A recent report (38) suggested that a sizeable fraction of CMVspecific CD4 ϩ T cells expresses KIR (and NKG2D). In these experiments, PBMC were stimulated with IL-2 in the presence or absence of CMV, and KIR (and NKG2D) expression on CD4 ϩ T cells was measured after 10 days.…”

Perforin level in CD4+ T cells from patients with systemic lupus erythematosus

“…The PRF1 gene is expressed primarily in NK cells and effector CD8 + T cells [31,32]. PRF1 is also expressed in a subpopulation of cytotoxic CD4 + T cells, which may combat various pathogens (33)(34)(35)(36)(37)(38)(39). An increased number of cytotoxic CD4 + T cells has been observed in patients with multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and acute coronary syndromes [20][21][22][23].…”