Cellular immune responses and disease control in acute AIDS-associated Kaposi's sarcoma

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) specific T cell responses and KSHV viremia were analyzed in seven HIV-infected patients with active Kaposi's sarcoma lesions who initiated highly active antiretroviral therapy, and were compared between patients with improved Kaposi's sarcoma and those with progressive Kaposi's sarcoma requiring further systemic chemotherapy. Patients with controlled Kaposi's sarcoma disease demonstrated undetectable Kaposi's sarcoma viremia together with KSHV-specific CD8 T cells secreting interferon-gamma and tumor necrosis factor-alpha, whereas progressors showed increasing viremia with weak or no T-cell responses. These data point toward a potential role of KSHV-specific immunity in the control of AIDS-associated Kaposi's sarcoma.

Monofunctional and Polyfunctional CD8+T Cell Responses to Human Herpesvirus 8 Lytic and Latency Proteins

“…A recent investigation found similar patterns of polyfunctional T cell responses in patients with multicentric Castleman's disease and healthy controls (13). Other investigators have reported that patients with nonprogressive KS have stronger and more frequent polyfunctional CD8 ϩ T cell responses than those with progressive KS (2). In the present study, we established that polyfunctional T cells specific for known and novel epitopes are present in the PBMC of healthy HHV-8-seropositive individuals.…”

“…ϩ T cell responses play a significant role in controlling HHV-8 infection and preventing development of KS (2,12). A central issue in understanding the CD8 ϩ T cell immunity in HHV-8 infection is the identification of MHC-I epitopes for the more than 80 open reading frames (ORFs) of the virus.…”

“…In one recent study, HHV-8 epitope-specific, polyfunctional T cells were detected in patients with multicentric Castleman's disease, but these cells did not differ in number from those in healthy controls (13). Another study has found that patients with controlled KS had HHV-8-specific CD8 ϩ T cells that secreted IFN-␥ and tumor necrosis factor alpha (TNF-␣) but that patients with progressive disease had weaker and less polyfunctional CD8 ϩ T cells (2). HHV-8 epitope-specific monofunctional and polyfunctional T cell immunity could be important in development of vaccines that induce T cell responses that target these viral epitopes.…”

Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex

“…Hence, a disruption of the RFX complex by LANA may result in a reduced binding of NLRC5 to the MHC-I enhanceosome, thus leading to reduced expression of MHC-I genes as well. MHC-I antigen presentation is critical for the activation of CD8 ϩ T cells, which has also been shown to play an important role in controlling KSHV infections (75,76). The role of LANA in inhibiting MHC-I through this mechanism remains to be explored, but targeting of the RFX complex by KSHV appears to help the virus dodge both MHC-I and MHC-II antigen-presenting pathways and consequently evade CD4 ϩ T and CD8 ϩ T cell immunities simultaneously.…”

KSHV

“…Additionally, it was found that CD4+ and CD8+ T cells from KSHV-seropositive patients frequently recognize select groups of early lytic and late lytic KSHV genes (Robey et al, 2009). In a cohort of seven KSHV+/HIV+ KS patients on HAART, KSHV-specific immune responses were detected in six of the seven patients (Bihl et al, 2009). Interestingly, 100% of the non-progressor patients had KSHV-specific CD8+ cytotoxic T lymphocytes (CTLs) that simultaneously secreted IFNγ and TNFα in response to KSHV antigen whereas only 60% of the patients with progressive disease had a CD8+ CTL response (Bihl et al, 2009).…”