TREC+ lymphocytes and IL-7 system in CD4-exploders, a group of HAART-treated, HIV+ patients with an optimal reconstitution of the CD4+ T cell pool.
Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1479)
Mussini C, Pinti M, Borghi V, Nasi M, Monterastelli E, Troiano L, Moretti L, Amorico G, Esposito R, Cossarizza A Azienda Policlinico, Modena, Italy
Among a population of more than 500 HIV-infected patients treated with highly active antiretroviral therapy (HAART), we found 6 individuals who experienced a nadir of less than 85 CD4+ cells/ é L (range: 11-84), had major opportunistic infections (4 out of 6), started HAART in 1996 or 1997, and showed a rapid and relevant CD4+ lymphocyte increase, regardless of virological control (actual HIV-RNA plasma levels: 870-2140 copies/mL). This increase (in all cases, CD4+ T cells were ≥870 cells/ é L), still present after 5 years, was mainly due to the production of virgin T cells (CD45RA+,CD62L+,CD95-). We defined these patients as "CD4-exploders" and analyzed some crucial characteristics of their immune system. High levels of lymphocytes possessing the T cell receptor rearrangement excision circles (TREC, detected by competitive-quantitative PCR) were found among CD4+ or CD8+ T cells, whose V[beta] T cell repertoire was normal (by flow cytometry and CDR3 lenght analysis). However, chest-computed tomography revealed a dramatic depletion of thymic lymphoid tissue. We measured plasma levels of interleukin (IL)-7 and the expression of IL-7 receptor [alpha] chain (IL-7R[alpha], analyzed either at the protein or the mRNA level) that were significantly high. Most CD4+ and CD8+ T cells expressed IL-7R[alpha], whose level was similar to that of healthy donors but markedly higher than those of individuals treated with the same therapy (but a minor CD4+ increase) or in AIDS patients. As TREC are present in "recent thymic emigrant" lymphocytes, and are thus related to thymus functionality, it can be hypothesized that in "CD4-exploders" the reconstitution of the T cell compartment due to HAART could occur extrathymically, and is in any case favoured by the upregulation of the IL-7/IL-7R system.
Keywords: AEGIS, Antiretroviral Therapy, Highly Active, Interleukin-7, T-Lymphocytes, Antigens, CD4, HIV Infections, Thymus Gland, CD4-Positive T-Lymphocytes, Receptors, Antigen, T-Cell, Receptors, Interleukin-7, Lymphoid Tissue, HIV Seropositivity, Flow Cytometry, Human, immunology
