MCCOIG C, SAAVEDRA J, PITCHER C, CAO Y, XU J, HATFIELD J, KEISER P, PICKER L, RAMILO O, VITETTA E; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. I-1904.
UT Southwestern Med Ctr, Dallas, TX
BACKGROUND: CD45RO[+] CD4[+] T cells are a major latent viral reservoir in HIV-infected individuals. Treatment of in vitro-generated HIV latently-infected cells with an anti-CD45RO immunotoxin (IT) eliminates >97% of CD45RO[+] T-cells, and this is associated with >95% suppression of p24 production following activation of the cells. 31% of CD4[+] memory cells (CD45RO[lo], CD27[lo], CD95[hi] producing IL-2, IL-4, IFN-g) are spared. In this study we evaluated the effect of the anti-CD45RO IT on CD4[+] T-cells obtained from HIV-infected individuals. METHODS: CD4[+] T cells were isolated from 16 HIV-infected individuals and were incubated with complete medium (CM), anti-CD25 IT, anti-CD45RO IT, or both ITs. After 6 days, cells were either cocultured in a limiting dilution with PHA-activated PBMCs or were analyzed by flow cytometry. RESULTS: Treatment with the anti-CD45RO IT reduced the frequency of HIV-infected T cells from 5-20 to <1/10[6] CD4[+] T cells. CM-treated cells contained 33 - 50% CD45RO[+] CD4[+] T cells and 52.8 - 66.8% CD4[+] memory T cells. Following treatment with the anti-CD45RO IT, the percentages of T cells were reduced to 1.5 - 3% and 6.2 - 13.9%, respectively. Similar reductions were observed with combinations of the anti-CD25 and the anti-CD45RO ITs (CD45RO[+]; 1.1 - 2%. memory cells; 4.5 - 19.3%). These cells remaining after IT treatment did not produce virus after coculture, suggesting that they were not infected with HIV. CONCLUSIONS: Treatment of CD4[+] T cells obtained from HIV-infected individuals with an anti-CD45RO IT, either alone or in combination with an anti-CD25 IT, eliminates CD45RO[+] HIV latently-infected cells and suppresses virus production but spares a significant percentage of memory CD4[+] T cells and all CD45RA[+] naive cells. This study confirms our previous results using in vitro HIV-infected PBMCs and suggests that this IT should be further evaluated for possible clinical use.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antigens, CD4
- Antigens, CD45
- Antiretroviral Therapy, Highly Active
- CASP4 protein, human
- Caspases
- Flow Cytometry
- HIV
- HIV Core Protein p24
- HIV Infections
- HIV Seropositivity
- Immunotoxins
- In Vitro
- Interleukin-2
- Receptors, Interleukin-2
- T-Lymphocytes
- drug therapy
- immunology
- therapy
Other ID:
UI: 102268673
From Meeting Abstracts