T cell expansions in lymph nodes and peripheral blood in HIV-1-infected individuals: effect of antiretroviral therapy

Objective: To evaluate dynamics in CD8 T cell expansions during highly acti ve antiretroviral therapy (HAART). Design: Various T cell subsets were isolated from blood and lymph nodes and analysed for T cell receptor (TCR) diversity. Methods: TCR complementarity determining region 3 (CDR3) spectratyping and single-strand conformation polymorphism (SSCP) analyses were performed in c ombination with sequencing to assess clonality of the subsets. Results: Strongly skewed CDR3 patterns in total CD8 cells and the CD8 subse ts CD45RO+CD27+ and CD45RO-CD27+ showed substantial dynamics in dominant CD R3 sizes, resulting in relative improvement of CDR3 size diversity in the f irst months of therapy. During sustained treatment, TCR diversity changed o nly moderately. SSCP profiles confirmed oligoclonality of TCR CDR3 perturba tions. Various dominant CDR3 sizes for CD4 and CD8 T cells present in lymph nodes, but not in peripheral blood mononuclear cells, before the start of therapy emerged in peripheral blood early during therapy. Conclusions: HAART induces substantial changes in CD8 TCR diversity, eventu ally resulting in improvement of the repertoire. Clonal expansions observed in lymph nodes before therapy were observed in peripheral blood after ther apy, suggesting that recirculation of CD4 and CD8 T cells from lymph nodes contributes to the early T cell repopulation. Decreased immune activation a nd possibly naive T cell regeneration subsequently decreased clonal expansi ons and perturbations in the CD8 TCR repertoire. (C) 2001 Lippincott Willia ms & Wilkins.