IL-2 therapy and thymic production of naive CD4 T cells in HIV-infected patients with severe CD4 lymphopenia.
OBJECTIVE
IL-2 therapy increases memory and naive CD4 T cells in HIV-infected patients, but its effect on thymopoiesis is unknown. To investigate this effect, we quantified T-cell receptor rearrangement excision circles (TREC) in CD4 T cells from lymphopenic AIDS patients treated with highly active antiretroviral therapy and IL-2.


METHODS
CD4 cell subsets were evaluated by flow cytometry using anti-CD45RO/RA, CD62L, Ki67 and CD95 monoclonal antibodies. The proportion of recent thymic emigrant had been quantified by a real-time polymerase chain reaction assay for signal joint TREC in peripheral blood mononuclear and purified CD4 T cells.


RESULTS
At initiation of IL-2, TREC copies/microl of blood were correlated with naive T cell numbers and age. Both naive and TREC numbers/microl significantly increased over time in all patients, with a wide range of TREC increases. Higher percentages of CD4+CD45RO-negative cells positive for the Ki67 cell-cycle marker were found in patients with a low TREC increase, but remained stable under IL-2. TREC and naive cell recovery were correlated; they also correlated with the numbers of TREC and naive cells at the start of IL-2, and with age, suggesting a thymic origin for naive T-cell recovery. A mathematical model showing the linear recovery of naive cells and TREC under IL-2 also strongly suggested that a naive T-cell increase reflects thymic export and involves little net death and proliferation.


CONCLUSIONS
Although we cannot rule out a mechanism of altered proliferation or death rate, the thymus plays an important role in the long-term recovery of naive T cells under IL-2 therapy.
Carcelain
Guislaine
G
Laboratoire d'Immunologie Cellulaire, Inserm U543, Paris, France.
Saint-Mézard
Pierre
P
Altes
Hester Korthals
HK
Tubiana
Roland
R
Grenot
Pierre
P
Rabian
Claire
C
de Boer
Rob
R
Costagliola
Dominique
D
Katlama
Christine
C
Debré
Patrice
P
Autran
Brigitte
B
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003131:Combined Modality Therapy; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000628:therapy* / Q000821:virology; D008875:Middle Aged; D011379:Prognosis; D013950:Thymus Gland / Q000276:immunology*
D007376:Interleukin-2