Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.
BACKGROUND
HIV-1(+) individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+) T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.


RESULTS
CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+) individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+) patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.


CONCLUSIONS
Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.
Department of Immunology, Imperial College London, Chelsea & Westminster Hospital, London, United Kingdom.
Samantha J
SJ
Westrop
Nadeem A
NA
Qazi
Jeffrey
J
Pido-Lopez
Mark R
MR
Nelson
Brian
B
Gazzard
Frances M
FM
Gotch
Nesrina
N
Imami
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D015488:HIV Antigens / Q000276:immunology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D013950:Thymus Gland / Q000276:immunology* / Q000821:virology*; D013997:Time Factors; D014764:Viral Proteins / Q000276:immunology
D015488:HIV Antigens; D010455:Peptides; D014764:Viral Proteins