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Detection and characterization of a vigorous, HIV specific CD4+ lymphocyte proliferative response.

Rosenberg E, Billingsley J, Kalams S, Walker B; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 4th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 4th 1997 Wash DC. 1997 Jan 22-26; 4th: 205 (abstract no. 760).

Massachusetts General Hospital, Boston, MA.

Objective: To determine the characteristics of an HIV-1 specific CD4+ proliferative response in a long-term nonprogressor with a normal CD4 count, undetectable viral load and no evidence of disease. Methods: Patient is a long-term nonprogressor infected for 16 years, with an HIV-1 RNA viral load of less than 400 copies, a CD4 count of 1440 and strong in vivo activated and memory CTL. CD4 specific proliferative responses were measured to tetanus toxoid, gp160 and p24, using antigens from 3 different sources. Kinetics of proliferative responses were measured every 24 hours. Cytokine & chemokine production was measured using commercially available kits. Target epitopes were identified using synthetic HIV-1 p24 peptides. Results: A vigorous HIV specific proliferative response to p24 was observed, with a stimulation index (SI) as high as 121, and with a significant but lower response to gp160. Kinetic analysis in vitro revealed an HIV specific proliferative response as early as 24 hours, which peaked at 5 days. Cytokine and chemokine profiles were consistent with a Th-1 type pattern. Vigorous production of INF-gamma, MIP-1beta, MIP-1alpha, and to a lesser extent RANTES was detected. At least 6 immunodominant epitopes were identified in p24, all with SI's greater than 10 and the highest being 110. Conclusions: These data provide firm evidence that HIV-1 can induce a vigorous Th-1 type CD4 proliferative response in an asymptomatic, HIV-1 infected person with an undetectable viral load. This response was directed simultaneously at multiple HIV- specific targets. Further characterization of this robust immune response may have implications for immunotherapeutic interventions and vaccine development.

Publication Types:
  • Meeting Abstracts
Keywords:
  • AIDS Vaccines
  • Acquired Immunodeficiency Syndrome
  • Antigens, CD4
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes
  • Chemokine CCL5
  • Chemokines
  • HIV Infections
  • HIV Seropositivity
  • HIV-1
  • Humans
  • In Vitro
  • Macrophage Inflammatory Proteins
  • T-Lymphocytes, Cytotoxic
  • Viral Load
  • immunology
Other ID:
  • 97926762
UI: 102225288

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