HIV patients developing primary CNS lymphoma lack EBV-specific CD4+ T cell function irrespective of absolute CD4+ T cell counts.

Abstract

BACKGROUND:

In chronic HIV infection, antiretroviral therapy-induced normalization of CD4(+) T cell counts (immune reconstitution [IR]) is associated with a decreased incidence of opportunistic diseases. However, some individuals remain at risk for opportunistic diseases despite prolonged normalization of CD4(+) T cell counts. Deficient Epstein-Barr virus (EBV)-specific CD4(+) T cell function may explain the occurrence of EBV-associated opportunistic malignancy-such as primary central nervous system (PCNS) lymphoma-despite recovery of absolute CD4(+) T cell counts.

METHODS AND FINDINGS:

Absolute CD4(+) T cell counts and EBV-specific CD4(+) T cell-dependent interferon-gamma production were assessed in six HIV-positive individuals prior to development of PCNS lymphoma ("cases"), and these values were compared with those in 16 HIV-infected matched participants with no sign of EBV-associated pathology ("matched controls") and 11 nonmatched HIV-negative blood donors. Half of the PCNS lymphoma patients fulfilled IR criteria (defined here as CD4(+) T cell counts >or=500/microl blood). EBV-specific CD4(+) T cells were assessed 0.5-4.7 y prior to diagnosis of lymphoma. In 0/6 cases versus 13/16 matched controls an EBV-specific CD4(+) T cell response was detected (p = 0.007; confidence interval for odds ratio [0-0.40]). PCNS lymphoma patients also differed with regards to this response significantly from HIV-negative blood donors (p < 0.001, confidence interval for odds ratio [0-0.14]), but there was no evidence for a difference between HIV-negative participants and the HIV-positive matched controls (p = 0.47).

CONCLUSIONS:

Irrespective of absolute CD4(+) T cell counts, HIV-positive patients who subsequently developed PCNS lymphoma lacked EBV-specific CD4(+) T cell function. Larger, ideally prospective studies are needed to confirm these preliminary data, and clarify the impact of pathogen-specific versus surrogate marker-based assessment of IR on clinical outcome.

• Authors: Olivier Gasser, Florian K Bihl, Marcel Wolbers, Elisabetta Loggi, Ingrid Steffen, Hans H Hirsch, Huldrych F Günthard, Bruce D Walker, Christian Brander, Manuel Battegay, Christoph Hess, Swiss HIV Cohort Study
• Journal: PLoS medicine (PLoS Med) Vol. 4 Issue 3 Pg. e96 (Mar 27 2007) ISSN: 1549-1676 [Electronic] United States
• PMID: 17388662 (Publication Type: Comment, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-gamma

Topics

• Adult
• CD4-Positive T-Lymphocytes (cytology, virology)
• Case-Control Studies
• Central Nervous System Neoplasms (complications, virology)
• Chronic Disease
• Cytomegalovirus (metabolism)
• Female
• HIV Infections (complications)
• Herpesvirus 4, Human (metabolism)
• Humans
• Interferon-gamma (metabolism)
• Lymphoma (complications, virology)
• Male
• Middle Aged
• Viral Load