Polyfunctional CD4(+) and CD8(+) T cell responses to tuberculosis antigens in HIV-1-infected patients before and after anti-retroviral treatment.
Tuberculosis (TB) kills 2 million people per year and infection with HIV is the most potent known risk factor for progression to active TB. An understanding of the immune response to TB Ags in HIV-infected patients is required to develop optimal TB vaccines and diagnostics. We assessed polyfunctional (IFN-gamma(+)IL-2(+)TNF-alpha(+)) T cell responses to TB Ags in three groups of HIV-1-infected patients dependent on their TB status, CD4 counts, and anti-retroviral exposure. We found that although the proportion of IFN-gamma cells in response to TB Ags was higher in patients with low CD4 counts, the responding cells changed from a polyfunctional CD4(+) to a monofunctional CD8(+) response. The overall polyfunctionality of the cells was restored by 12 mo of anti-retroviral therapy and primarily involved CD4(+) T cells with an effector memory phenotype. These findings have major implications for diagnosis of TB and in vaccine development strategies for TB in HIV-1-infected patients.
Sutherland
Jayne S
JS
Medical Research Council Laboratories, Banjul, The Gambia, West Africa. jsutherland@mrc.gm
Young
James M
JM
Peterson
Kevin L
KL
Sanneh
Bakary
B
Whittle
Hilton C
HC
Rowland-Jones
Sarah L
SL
Adegbola
Richard A
RA
Jaye
Assan
A
Ota
Martin O C
MO
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000150:complications / Q000276:immunology; D055815:Young Adult
D044966:Anti-Retroviral Agents; D000942:Antigens, Bacterial; C072681:Mycobacterium tuberculosis antigens