Influence of HIV infection on cytomegalovirus-specific immunity: T-cell responses to pp65 and IE1 before and after HAART may reflect altered cytomegalovirus biology

Antivir Ther. 2011;16(4):565-75. doi: 10.3851/IMP1800.

Abstract

Background: Data are inconclusive whether treatment with HAART induces functional recovery of HIV-specific T-cells. Since the introduction of HAART, a marked decrease of cytomegalovirus (CMV) disease - for which untreated HIV-infected individuals are at increased risk - is observed, suggesting that this treatment influences CMV-specific T-cell immunity.

Methods: To study potential functional recovery of HIV- and CMV-specific T-cells, CD4(+) and CD8(+) T-cell responses were measured longitudinally after in vitro expansion using gag, pp65 and IE1 peptide pools, during HIV infection and after long-term HAART.

Results: HIV-specific T-cell function, measured by interferon (IFN)-γ production, was low after initiation of HAART. Interestingly, the cytotoxic function - measured by CD107a expression - of these T-cells temporarily increased after start of treatment, suggesting some functional recovery. The pp65-specific CD8(+) T-cell responses tended to decrease during HIV infection, whereas pp65-specific CD4(+) T-cell responses decreased upon treatment with HAART. Both pp65-specific CD4(+) and CD8(+) T-cell responses were low after initiation of HAART compared to healthy controls. By contrast, IE1-specific CD4(+) T-cell responses increased during the course of HIV infection. After initiation of HAART, IE1-specific T-cell responses decreased, but IE1-specific CD8(+) T-cells seemed increased compared to healthy controls.

Conclusions: This study suggests that HIV-infection leads to an altered CMV biology, affecting pp65- and IE1-specific T-cell responses in a different way, which is not restored by treatment with long-term HAART.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / virology
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Immediate-Early Proteins / immunology*
  • Male
  • Phosphoproteins / immunology*
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Viral Matrix Proteins / immunology*

Substances

  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa