Increased thymic output in HIV-negative patients after antiretroviral therapy.
OBJECTIVE
To determine the effects of antiretroviral therapy on thymic output independent of HIV infection.


METHODS
Thymic output was evaluated by quantifying signal joint T-cell receptor (TCR) recombination excision circles in peripheral blood lymphocytes from HIV-negative patients undergoing prophylactic antiretroviral therapy. Additionally, effects of the HIV protease inhibitor nelfinavir were assessed in vivo on TCR-induced death of murine double-positive thymocytes.


RESULTS
Five out of seven HIV-negative patients undergoing prophylactic antiretroviral therapy exhibited a dramatic increase (1-3 log10) in recent thymic emigrants containing signal joint TCR recombination excision circles while their peripheral T cell compartments remained relatively unaffected. None of the patients developed subsequent HIV infections. Interestingly, nelfinavir did not have significant effects on TCR-induced apoptosis of murine thymocytes in vivo.


CONCLUSIONS
Antiretroviral therapy augments thymic output independent of HIV. Furthermore, nelfinavir does not dramatically affect TCR-induced thymocyte death in mice, thus central tolerance remains intact.
Graham
Daniel B
DB
Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Bell
Michael P
MP
Huntoon
Catherine J
CJ
Weaver
Joel G R
JG
Hawley
Nanci
N
Badley
Andrew D
AD
McKean
David J
DJ
D000328:Adult; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000276:immunology; D016022:Case-Control Studies; D015658:HIV Infections / Q000517:prevention & control; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell