Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time.
BACKGROUND
T-cell immunity is thought to play an important role in controlling HIV infection, and is a main target for HIV vaccine development. HIV-specific central memory CD8(+) and CD4(+) T cells producing IFNgamma and IL-2 have been associated with control of viremia and are therefore hypothesized to be truly protective and determine subsequent clinical outcome. However, the cause-effect relationship between HIV-specific cellular immunity and disease progression is unknown. We investigated in a large prospective cohort study involving 96 individuals of the Amsterdam Cohort Studies with a known date of seroconversion whether the presence of cytokine-producing HIV-specific CD8(+) T cells early in infection was associated with AIDS-free survival time.


RESULTS
The number and percentage of IFNgamma and IL-2 producing CD8(+) T cells was measured after in vitro stimulation with an overlapping Gag-peptide pool in T cells sampled approximately one year after seroconversion. Kaplan-Meier survival analysis and Cox proportional hazard models showed that frequencies of cytokine-producing Gag-specific CD8(+) T cells (IFNgamma, IL-2 or both) shortly after seroconversion were neither associated with time to AIDS nor with the rate of CD4(+) T-cell decline.


CONCLUSIONS
These data show that high numbers of functional HIV-specific CD8(+) T cells can be found early in HIV infection, irrespective of subsequent clinical outcome. The fact that both progressors and long-term non-progressors have abundant T cell immunity of the specificity associated with low viral load shortly after seroconversion suggests that the more rapid loss of T cell immunity observed in progressors may be a consequence rather than a cause of disease progression.
Schellens
Ingrid M M
IM
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Borghans
José A M
JA
Jansen
Christine A
CA
De Cuyper
Iris M
IM
Geskus
Ronald B
RB
van Baarle
Debbie
D
Miedema
Frank
F
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
D016207:Cytokines; D007376:Interleukin-2; D010455:Peptides; D007371:Interferon-gamma