AEGiS-11IAC: Relationship between lymphocyte activation and cytokine production in blood and lymph node cells.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Relationship between lymphocyte activation and cytokine production in blood and lymph node cells.

Int Conf AIDS 1996 Jul 7-12; 11:213 (abstract no. Th.A.161)
Holodniy M, Mole L, Schulte M, Suni M, Ruitenberg J, Lalezari J, Maino V, Schnittman S; VA Palo Alto Health Care System, Palo Alto, CA. Fax: 415 858-3978. E-mail: hf.myh@forsythe.stanford.edu.

OBJECTIVE: To monitor lymphocyte activation and cytokine expression in peripheral blood (PB) mononuclear cells and lymph node (LN) derived cells, before and after zidovudine (ZDV) therapy in HIV seropositive individuals.

METHODS: HIV seropositive subjects who were drug naive, had blood taken and lymph node biopsies performed, before and 8 weeks after ZDV monotherapy. PB and LN CD3+/CD4+ and CD3+/CD8+ cell activation was measured by CD69 expression after stimulation with CD2/CD2R, pokeweed mitogen (PW) and staphylococcal enterotoxin B(SEB) using flow cytometry techniques. Constitutive and stimulated expression of intracellular IL-2, IL-4, and gammaIFN using phorbol ester and ionomycin, were measured in PB and LN CD3+/CD8+ and CD3+/CD8- cells using flow cytometry.

RESULTS: Baseline CD69 expression in CD4+ and CD8+ cells was significantly greater in LN compared to PB. Stimulation of PB CD4+ and CD8+ cells, but not LN cells, resulted in a marked increase in CD69 expression. After 8 weeks of ZDV therapy, only PB CD4+ cells, demonstrated a significant increase in activation following CD2/CDR and SEB stimulation. There was no constitutive expression of these cytokines in both PB and LN cells. Stimulation resulted in significantly increased IL-2 and gammaIFN expression, and to a much lesser degree IL-4, in both PB and LN. ZDV resulted in decreased IL-2 and gammaIFN stimulated expression in both PB and LN cells.

CONCLUSIONS: This data suggests that a significantly greater proportion of LN cells are in an activated state without exogenous stimuli. After stimulation, PB cell activation levels are significantly increased, PB cell cytokine expression parallels that found in LN cells. Although constitutive expression of all cytokines was absent, stimulation resulted in a TH1 type pattern, in both PB and LN cells. ZDV therapy results in increased PB CD4+ cell activation and decreased expression of IL-2 and gammaIFN in both PB and LN cells. These findings have important implications for further immunologic and pathogenesis based studies.

Keywords: AEGIS, Lymphocyte Activation, Cytokines, Lymph Nodes, Antigens, CD3, Antigens, CD8, CD8-Positive T-Lymphocytes, Antigens, CD4, CD4-Positive T-Lymphocytes, Antigens, Differentiation, T-Lymphocyte, Antigens, CD, Antigens, CD2, Interleukin-2, Th2 Cells, Th1 Cells, T-Lymphocyte Subsets, Zidovudine, Flow Cytometry, T-Lymphocytes, Leukocytes, Mononuclear, Cells, Leu-23 antigen, blood, immunology, ICA11

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