In some individuals, infection with HIV induces the secretion of TGF-1 by CD+8+ T cells, which inhibits the antiviral IFN- response.
To combat viral infections, viral-specific CD8+ cytotoxic T lymphocytes (CTLs) are generated that kill infected cells and release antiviral cytokines, such as interferon- (IFN-). Early in HIV infection, HIV-specific T-cell responses are difficult to detect in some infected people, even though individuals are immunologically normal at this stage of infection. The reason for this lack of immune activity is unknown. Garba and colleagues now report in the Journal of Immunology that in some individuals, infection with HIV induces the secretion of transforming growth factor-1 (TGF-1) by CD8+ T cells, which inhibits the antiviral IFN- response.
To investigate the antiviral IFN- responses of HIV-infected individuals, the authors co-cultured peripheral blood mononuclear cells (PBMCs) from these patients with transformed B-cell lines that had been infected with a recombinant vaccinia virus that expressed the HIV proteins Gag, Pol and Env. PBMCs from 25% of the HIV-infected individuals failed to respond to stimulation with HIV antigens, and these patients were categorized as 'suppressors' by the investigators (rather than 'responders', who did produce IFN-).
What causes the reduced IFN- responses in suppressors? The authors measured the level of TGF-1 in the PBMC cultures. They found that CD8+ T cells from suppressors produced a greater amount of TGF-1 in response to HIV antigens than did responders. The addition of anti-TGF-1 antibodies to the cultures restored IFN- responses, which confirms that IFN- responses are suppressed by TGF-1.
These results provide an explanation for why some people fail to raise effective HIV-specific CTL responses against HIV infection, and highlight TGF-1-blocking therapy as a potential treatment for some HIV-infected individuals.
Jenny Buckland
References
Garba, M. L. et al. HIV antigens can induce TGF-1-producing immunoregulatory CD8+ T cells. J. Immunol.168, 2247–2254 (2002) | PubMed |
Lieberman, J. et al. Dressed to kill? A review of why antiviral CD8 T lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection. Blood98, 1667–1677 (2001) | PubMed |
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