HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation.
The supply of naive T cells by the thymus normally requires precursor T cell proliferation within the thymus and would be particularly important in the setting of HIV infection when both naive and memory T cells are progressively depleted. As a robust, quantitative index of intrathymic proliferation, the ratio of different T cell receptor excision circles (TRECs), molecular markers of distinct T cell receptor rearrangements occurring at different stages of thymocyte development, was measured in peripheral blood-mononuclear cells (PBMCs). This ratio has the virtue that it is a "signature" of thymic emigrants throughout their entire life and, thus, can be measured in peripheral cell populations that are easy to obtain. Using the new assay, we evaluated the effect of HIV infection on intrathymic precursor T cell proliferation by longitudinal analysis of PBMCs from recently infected individuals. Our findings reveal a substantial reduction in intrathymic proliferation. The analysis also indicates the existence of a compensatory mechanism acting to sustain the numbers of recent thymic emigrants (RTEs) in the periphery.
Dion
Marie-Lise
ML
Laboratoire d'Immunologie, Centre de Recherches du CHUM, Hôtel-Dieu, Montréal, Québec H2X 1P1, Canada.
Poulin
Jean-François
JF
Bordi
Rebeka
R
Sylvestre
Myriam
M
Corsini
Rachel
R
Kettaf
Nadia
N
Dalloul
Ali
A
Boulassel
Mohamed-Rachid
MR
Debré
Patrice
P
Routy
Jean-Pierre
JP
Grossman
Zvi
Z
Sékaly
Rafick-Pierre
RP
Cheynier
Rémi
R
D000375:Aging / Q000276:immunology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D049109:Cell Proliferation; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D006801:Humans; D007958:Leukocyte Count; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology* / Q000821:virology
D019380:Anti-HIV Agents; D011948:Receptors, Antigen, T-Cell