Increasing CD4+ T cells specific for tuberculosis correlate with improved clinical immunity after highly active antiretroviral therapy.
Treatment advances have led to dramatic clinical improvements for patients with HIV-1 infection. These clinical improvements reflect treatment-related improvements in immune function, which are most striking in individuals who develop exaggerated immune inflammatory responses to occult opportunistic infections. The mechanisms accounting for these exaggerated immune responses are unknown. To gain insight into these mechanisms, we intensively studied a subject untreated for disseminated tuberculosis and HIV-1 coinfection who then began treatment for both diseases. We examined the changing frequencies of Mycobacterium tuberculosis (MTB)-specific CD4(+) T cells that produced interferon gamma (IFN-gamma) after short-term stimulation with MTB antigen, and we compared these frequencies with those in HIV-1-seronegative subjects with and without prior exposure to MTB antigens. For the HIV-1/MTB-coinfected subject, the proportion of peripheral blood CD4(+) T cells expressing MTB-specific IFN-gamma was 8.6% at 11 days, 11% at 33 days, and 33% at 95 days after starting treatment for HIV-1. CD4(+) IFN-gamma(+) T cells had a CD45RA(-)CD62L(-) (effector memory) phenotype and most coexpressed interleukin 2. Median frequencies of CD4(+) IFN-gamma(+) T cells from six subjects without and nine subjects with prior exposure to MTB antigens were 0.06 and 0.46%, respectively. We conclude that individuals starting treatment for disseminated tuberculosis and HIV-1 coinfection can accumulate remarkably large numbers of MTB-specific CD4(+) T cells in the peripheral blood. The rapid expansion of antigen-specific effector CD4(+) T cells is one mechanism to explain immediate improvements in clinical immunity after HIV-1 treatment. This mechanism provides a theoretical framework to understand the unusual inflammatory responses recently reported to occur after starting HIV-1 treatment.
Hengel
Richard L
RL
Division of Infectious Diseases, Department of Medicine, Georgetown University School of Medicine, Washington, D.C. 20057, USA. rhengel@nih.gov
Allende
Maria C
MC
Dewar
Robin L
RL
Metcalf
Julia A
JA
Mican
JoAnn M
JM
Lane
H Clifford
HC
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy*; D019562:Viral Load
D007371:Interferon-gamma