T cell response to viral antigens in adults and children with common variable immunodeficiency and specific antibody deficiency

Abstract

SummarySeveral T cell abnormalities have been described in common variable immunodeficiency (CVID), a B cell disorder of mainly unknown origin. A subset of CVID patients suffers from frequent reactivations of herpes viruses. We studied T cell function in CVID [and in a subset of paediatric patients with specific antibody deficiency (SAD)] by measuring T cell proliferation and cytokine production in response to herpes virus-antigens in paediatric CVID patients (n = 9) and paediatric SAD patients (n = 5), in adult CVID patients (n = 14) and in healthy controls. Paediatric CVID patients, but not SAD patients, displayed moderately increased CD8+ T cell proliferation in response to cytomegalovirus, human herpes virus type 6B (HHV6-B) and herpes simplex virus compared to controls. CD8 + T cell responses in adult CVID patients tended to be increased in response to cytomegalovirus and herpes simplex virus. In response to stimulation with herpes virus antigens, the proinflammatory cytokines interleukin (IL)-1b, IL-6, tumour necrosis factor (TNF)-a and interferon inducible protein (IP)-10 were produced. Overall, no major differences were detected in cytokine production upon stimulation between patients and controls, although higher IL-10 and IL-12 production was detected in paediatric patients. In conclusion, cellular immunity against herpes virus antigens appears undisturbed in CVID patients, although defects in subpopulations of CVID patients cannot be excluded.

Cytokine and cellular responses to human herpesvirus‐6B in patients with B‐acute lymphoblastic leukemia

“…Furthermore, in our study we observed the same frequencies of HHV‐6‐specific CD4+ T cells regardless of presence or absence of HHV‐6 DNA in blood. Similarly, CD4+ T cell proliferation in response to HHV‐6 in pediatric patients with common variable immunodeficiency is comparable to that observed in controls .…”

“…In patients with common variable immunodeficiency, the pro‐inflammatory cytokines IL‐6 and TNF‐α are produced in response to stimulation with HHV‐6 antigens. Overall, no major differences between patients and controls in cytokine production upon stimulation were detected . Moreover, an increase in IL‐6 production has been demonstrated in patients with HHV‐6 infection in previous studies , whereas another study reported strong of production TNF‐α, but not of IL‐6, by PBMCs from healthy donors stimulated with HHV‐6 .…”

“…Few studies have focused on analyzing the immune response to HHV‐6 infection. Analysis of T‐cell responses to HHV‐6 has indicated the presence of a T‐cell proliferative response against HHV‐6 infection . Others studies have characterized HHV‐6 specific CD4+ and CD8+ T cells .…”

Immune response to HHV-6 and implications for immunotherapy

“…T cell responses have been reported to be higher in HSCT patients [42], but few studies have focused on this population. Despite the low frequency of responding T cells in healthy adults, strong CD4+ and CD8+ T cell proliferative responses are observed [43–45], primarily restricted to memory cells. Proliferation of HHV-6-specific T cells in response to viral antigen allows these low-frequency T cell populations to be expanded in vitro for detailed study.…”

Lymphoid Proliferations of Indeterminate Malignant Potential arising in Adults with Common Variable Immunodeficiency Disorders: Unusual Case Studies and Immunohistological Review in the Light of Possible Causative Events

“…There is the possibility that these uncommon patients have an autosomal recessive form of combined immune deficiency since there is an over-representation of consanguinity in this group [14]. There are reports of defects of antigen presentation and cellular immunity in CVIDs and at least half of patients with CVID have circulating T cells specific for epitopes derived from CMV and/or EBV [15, 16]. Whether this is relevant to the development of MALT lymphomas in CVID patients remains to be seen.…”