AEGiS-11IAC: TH1- and TH2-like cytokine secretion and proliferative responses in children born to HIV+ women.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

TH1- and TH2-like cytokine secretion and proliferative responses in children born to HIV+ women.

Int Conf AIDS 1996 Jul 7-12; 11:213 (abstract no. Th.A.160)
Sirera R, Bayona A, Carbonell F, Otero MC, Perez-Tamarit A, Canosa C, Gonzalez-Molina A; Inmunologia Exp., C.Investigacion Hospital La Fe, Valencia, Spain.

OBJECTIVE: To establish the relationship between the in vitro production of lympho-monokines and the lymphocyte proliferative responses with the number of circulating cells from HIV-1 positive children born to HIV-1(+) mothers.

METHODS: In a long term follow-up (11 years), 77 HIV-1 positive and 167 HIV-1 negative (SR; CDC, 1994) children born to HIV-1 positive mothers have been evaluated. Lymphocyte subpopulations were characterized by flow cytometry. For functional studies whole blood cells (WBC) without plasma were washed twice, adjusted to 106 leukocytes/ml in supplemented RPMI 1640 and seed in microcultures. Immunocompetent cells were stimulated with PHA or anti-CD3. By ELISA, Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-5, IL-6 and IL-10) cytokines, TNF-alpha and sCD23 were measured in kinetic cell free supernatants collected up to 96h. In parallel cultures, the blastogenic capacity of T cells was analyzed by 3H-thymidine incorporation at day 4.

RESULTS: In WBC cultures from HIV-1(+) children significantly low proliferative responses to anti-CD3 and PHA stimulation were observed (60 and 40% respectively). However, in HIV-1 infected children with CD4 per microliter greater than 500, IL-2, IFN-gamma, IL-6 and TNF-alpha were detected increased in PHA and/or anti-CD3 supernatants. Furthermore, Th2-like cytokines were mainly increased in up to 60% of HIV-1(+) children with CD4 per microliter less than 200. PHA-induced sCD23 secretion was lower in HIV(+) than in SR children and independent of CD4 cell counts.

CONCLUSIONS: Whole blood cultures are appropriate to study cytokine secretion patterns and proliferative responses in children. During the course of HIV infection in children a deficient DNA synthesis induced by anti-CD3 was the earliest functional abnormality observed in HIV(+) children even with normal CD4 level. The hypersecretion of cytokines (i.e. IL-2) and the low proliferative responses observed in HIV(+) children might suggest a defect in the expression of cytokine receptors and/or defects in its signal transduction pathways. Th2-like cytokines could be dominant in late stages of HIV-1 infection.

Keywords: AEGIS, Cytokines, HIV-1, HIV Infections, CD4 Lymphocyte Count, Interleukin-2, Interleukin-10, Interleukin-4, Bodily Secretions, Phytohemagglutinins, HIV Seropositivity, T-Lymphocytes, Antigens, CD4, Interleukin-6, Interleukin-5, Human, Female, Child, In Vitro, secretion, ICA11

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