Following up on a prior post about the link between loss of T cell responses to tuberculosis and reactivation TB disease, a new paper in the Journal of Immunology reports on the functionality of TB-specific T cell responses before and after antiretroviral treatment (ART). The study - led by Jayne S. Sutherland from the Medical Research Council Laboratories in The Gambia - reports that, in untreated individuals, the CD4 T cell response to TB declines as peripheral blood CD4 T cell counts fall. Among individuals with CD4 T cell counts over 500, the response to purified protein derivative (PPD) consisted of CD4 T cells making the cytokines TNF alpha (TNF-a) and interferon gamma (IFN-g), along with CD8 T cells making either one of these two cytokines. In contrast, individuals with less than 200 CD4 T cells showed an almost complete loss of CD4 T cell responses and a shift to CD8 T cell responses (the majority making interferon gamma alone).
Six months after ART initiation, PPD-specific CD4 T cell responses returned and the proportion of cells producing both TNF-a and IFN-g increased compared to pre-treatment baseline. The proportion of CD4 T cells making the cytokine IL-2 also increased among cells specific for PPD and another TB antigen, the ESAT-6/CFP-10 fusion protein. Levels of CD8 T cell responses to TB did not change significantly. The researchers note that this change in the quality of the response is likely to be important because studies have shown that CD4 T cells make a critical contribution to immune protection against TB.
Published online April 30, 2010
The Journal of Immunology, 2010, doi:10.4049/jimmunol.1000399
Jayne S. Sutherland, James M. Young,1 Kevin L. Peterson, Bakary Sanneh, Hilton C. Whittle, Sarah L. Rowland-Jones,2 Richard A. Adegbola,3 Assan Jaye, and Martin O. C. Ota
Medical Research Council Laboratories, Banjul, The Gambia, West Africa
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-+IL-2+TNF-+) 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- 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.