IFN-γ Promotes Generation of IL-10 Secreting CD4+ T Cells that Suppress Generation of CD8 Responses in an Antigen-Experienced Host

Abstract

Ags characterizing tumors or chronic viral infection are generally presented to the host immune system before specific immunotherapy is initiated, and consequent generation of regulatory CD4+ T cells can inhibit induction of desired effector CD8 T cell responses. IL-10 produced in response to ongoing Ag exposure inhibits generation of CD8 T cells in an Ag-experienced host. We now show that this IL-10 is produced by Ag experienced CD4+ glucocorticoid-induced tumor necrosis factor receptor+ T cells that also secrete IFN-γ upon antigenic stimulation, that IL-10 secretion by these cells is enhanced through IFN-γ signaling, and, unexpectedly, that IFN-γ signaling is required for inhibition of generation of Ag-specific CD8 T cell responses in an Ag-experienced host. Systemic inhibition of both IL-10 and IFN-γ at the time of immunization may therefore facilitate induction of effective immunotherapeutic responses against tumor specific and viral Ags.

Influenza matrix 1‐specific human CD4+FOXP3+ and FOXP3− regulatory T cells can be detected long after viral clearance

“…Rather, an increased antigen dose led to higher suppression. This fits well with a recent study on CD4 1 IL-10/IFN-g-producing T cells in mice showing that IFN-g signaling enhanced the production of IL-10 and had an essential role in the inhibitory capacity of these T cells [27], suggesting that the observed switch to dual production in our Treg clones may reflect increased suppressive capacity. Notably, the T-cell clones analyzed displayed a consistent phenotype for at least 1-2 years in terms of suppressive capacity.…”

New approaches to emergency prevention and treatment of viral infections by the example of tick-borne encephalitis and influenza

“…Кроме того, установ-лено статистически значимое повышение содержания в супернатантах ИФН-гамма (p = 0,012) между 1 и 2 визита-ми на фоне применения Йодантипирина, с дальнейшим динамическим снижением уровня этого показателя до исходных значений к визиту 3 (p = 0,06), что соответство-вало смешанному T-хелпер 1/T-хелпер 2-типу, адекватному варианту иммунного ответа на вирусную инфекцию [12].…”

Hepatitis B Surface Antigen-based Vaccines for Human Neoplastic Disease

“…When comparing the CTL response from mice with established lung metastasis and treated with pE7HBE6 or with combined pE7 ko HBE6 and pE7HBE6 ko vaccine (Figure 5.6C (Herd et al, 1997;Azoury-Ziadeh et al, 2001). It is likely that TC-1 tumours have active immune-suppressive mechanisms including tolerance induction due to endogenously E6 and E7 activity (Doan et al, 1999;Barnard et al, 2000;Kotecha et al, 2003;Lepique et al, 2009;Liu et al, 2009;Narayan et al, 2009). …”

“…If infection is not cleared, persistence results in chronic infection and disease with possible progression to neoplasia (Tindle, 2002;O'Brien & Campo, 2003). HPV utilises a number of evolved mechanisms to avoid the immune system (De Andrea et al, 2007;Stanley, 2008;Hypes et al, 2009;Liu et al, 2009;Narayan et al, 2009 that are required to prime naïve CTL populations (Bal et al, 1990), therefore HPV proteins expressed in keratinocytes are presented to the host immune system in the absence of an inflammatory signal, which induces tolerogenic rather than immunogenic responses (Doan et al, 1998;Azoury-Ziadeh et al, 2001). The activity of E6 and E7 can repress the expression of Type 1 interferons, leading to antigen tolerance (Tindle, 2002).…”

“…Protection against TC-1 tumour challenge is mediated by CD8 + T-cells Indrova et al, 2008;Rowley et al, 2008;Chuang et al, 2009b;Li et al, 2009) and is assisted by NK cells (Indrova et al, 2008;Rowley et al, 2008) however, there is conjecture over the requirement of CD4 + T-cells in the prevention of TC-1 tumour growth Huang et al, 2007;Liu et al, 2009). To examine whether CD4 + T-cells were required for pE7HBE6-mediated protection against TC-1 tumour challenge, mice (n=16) were immunised twice with 100µg of pE7HBE6, with a two week interval.…”