CD8⁺Cytotoxic T Lymphocyte Responses to Lytic Proteins of Human Herpes Virus 8 in Human Immunodeficiency Virus Type 1–Infected and –Uninfected Individuals

Abstract

T cell immunity to lytic proteins of herpesviruses is important in host control of infection. We have characterized the cytotoxic T lymphocyte (CTL) response to 5 human herpesvirus 8 (HHV-8) homologues of lytic proteins in HHV-8-seropositive individuals. HLA class I-restricted, CD8(+) CTL responses to >/=1 HHV-8 lytic protein were detected in all 14 HHV-8-seropositive study subjects tested, with or without human immunodeficiency virus type 1 (HIV-1) infection, but not in any of 5 HHV-8-seronegative individuals. Seven of these study subjects with both HHV-8 and HIV-1 infection had greater anti-CTL reactivity to glycoprotein H (open-reading frame 22) than did the 7 study subjects infected only with HHV-8. Moreover, there was a strong, inverse correlation between HIV-1 load and glycoprotein H-specific CTL lysis in the study subjects infected with both viruses. CTL reactivity to HHV-8 lytic proteins may be involved in host control of HHV-8-related diseases, such as Kaposi's sarcoma.

Effect of highly active antiretroviral therapy on survival among HIV‐infected men with Kaposi sarcoma or non‐Hodgkin lymphoma

“…34 Support for this hypothesis is that there is a CD8 ϩ cytotoxic T-cell response to KSHV that is lower among those infected with HIV-1. [35][36][37] Jung et al 38 found that HAART may enhance efficiency of KS cancer treatment. For example, patients on HAART were able to sustain longer cycles of chemotherapy and ultimately discontinuation of therapy without experiencing relapse.…”

Identification of cytotoxic T lymphocyte epitopes of human herpesvirus 8

“…The peptides derived from kaposin A were a 10-amino-acid-long peptide (amino acids [16][17][18][19][20][21][22][23][24][25] and its shorter version (amino acids [17][18][19][20][21][22][23][24][25]. Since the decamer peptide is reported to have a higher estimated half-time dissociation score and contains both potential epitopes, it was selected for further studies.…”

“…[18][19][20][21] At present, very little is known on the immune control of HHV-8 in infected individuals, however, there is evidence indicating the presence of CTL responses specific for latent and lytic antigens. [22][23][24] Since HHV-8-derived epitopes may be regarded as a potential target of specific immunotherapies for the treatment/prevention of HHV-8-associated malignancies, we sought to characterize CTL peptide antigens derived from HHV-8 antigens.…”

“…22,23 HLA-A2 was chosen since it is the most common HLA class I molecule in humans, and therefore represents an important restriction element for CTL-based immunotherapy. In addition, a large amount of information on the requirements for HLA-A2-peptide interactions is available, including the crystallographic structure of MHC-peptide complexes 25 and naturally processed peptide sequence motifs.…”

γδ+ T Cells Involvement in Viral Immune Control of Chronic Human Herpesvirus 8 Infection

“…The increased incidence of these diseases in immunocompromised individuals suggests that host immune control may be essential in preventing HHV-8-associated diseases (2). Several studies have demonstrated the anti-HHV-8 specificity of TCR ␣␤ ϩ CD8 ϩ CTL (3)(4)(5)(6)(7)(8)(9)(10). HHV-8 specific CTL responses to latent and lytic viral proteins have been detected during primary HHV-8 infection (11).…”