AEGiS-11IAC: Cellular immune responses in peripheral blood and lymph nodes during early HIV-1 infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Cellular immune responses in peripheral blood and lymph nodes during early HIV-1 infection.

Int Conf AIDS 1996 Jul 7-12; 11:12 (abstract no. We.A.382)
Musey LK, Hu YX, Schacker T, Hughes J, Corey L, McElrath MJ; University of Washington, School of Medicine, Seattle, WA. Fax: 1-206-4178. E-mail: luwy@u.washington.edu.

OBJECTIVES: To identify the patterns of cellular immune responses in peripheral blood and lymph nodes during the early phases of HIV-1 infection and to correlate these responses in a large patient cohort with changes in CD4 count, viral load, and clinical disease.

METHODS: Thirty-nine patients with documented recent HIV-1 infection underwent clinical evaluation and venipuncture every 4 weeks over a mean follow-up of 15 months for analysis of T helper and CTL responses, CD4 count, and plasma HIV-1 RNA by bDNA assay. Lymphoproliferative (LP) responses to mitogen (PHA), non-HIV-1 recall (candida and tetanus) and HIV-1 antigens were performed, and expressed as stimulation indices (S.I.). Activated CTLs were determined by direct assay using undepleted, CD4+ and CD8+ enriched PBMC. Memory CTL were measured by limiting dilution analysis (LDA) after in vitro stimulation of effectors. A comparative analysis of the LP responses and memory CTL in the peripheral blood and lymph node was also performed among 14 patients.

RESULTS: LP responses were initially depressed to mitogen, recall and HIV-1 antigens. A significant rebound in responses to mitogen and recall antigens was observed 6-8 months after infection. However, T helper responses to HIV-1 antigens were rarely demonstrated (S.I. greater than 3 in 6/56 to gp 120 and 4/45 to p24). Activated circulating CTLs were detected in 16/23 (70%) at study entry, were mediated primarily by CD8+ effectors (9/18, 50%) and were directed most often to envelope (15/23, 65%). Memory CTL, recognizing autologous targets expressing HIV-1 Env, Gag, and/or Pol were found in 28/30 (93%) of the patients, with pCTL frequency ranging from 1 to 446 per 106 PBMC. An initial fall in the pCTL frequency was observed from entry to 6-8 months, followed by a stabilization. Similar LP and pCTL responses were noted in lymph nodes and blood. Correlations of these immune responses with changes in viral load and CD4+ cell count are currently under investigation.

CONCLUSIONS: HIV-1 infection induces a vigorous CTL response soon after exposure. Of the three structural gene products, both activated and memory CTL predominantly recognize Env-expressing targets. Despite the vigorous effector response, T helper dysfunction occurs early in infection in both blood and lymph nodes, and with rare exception persists over the ensuing years.

Keywords: AEGIS, HIV-1, HIV Antigens, HIV Infections, Viral Load, CD4 Lymphocyte Count, Lymph Nodes, Antigens, CD4, Antigens, CD8, Cytotoxicity, Immunologic, Immunity, HIV Seronegativity, Lymphocyte Activation, In Vitro, Human, immunology, ICA11

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WeA382