Author(s): Nattawat Onlamoon [*] aff1 aff2 , Vajee Petphong aff1 aff3 , Kasama Sukapirom aff1 , Siyu Wang aff1 aff3 , Palanee Ammaranond aff4 , Kovit Pattanapanyasat aff1 aff2
CD4+ T lymphocytes; anti-CD3/28 coated beads; in vitro cell expansion; HIV-infected patients
Autologous transfers of CD4+ T lymphocytes from in vitro expansion with anti-CD3/28 coated beads were conducted successfully in both HIV-infected patients and SIV-infected nonhuman primates. A study in HIV-infected patients demonstrated the safety and feasibility of infusing anti-CD3/28 expanded CD4+ T lymphocytes in patients with intermediate-stage HIV infection. The results showed a transient decrease in viral load and an initial increase in CD4 + T lymphocyte number as well as a persistent increase in CD4+ T lymphocyte that express Ki-67 [1 ]. A follow-up study in these patients demonstrated an increase in TCR diversity and an increased proliferative response to alloantigen [2 ]. The results suggested that autologous transfers of anti-CD3/28 expanded CD4+ T lymphocytes may provide a mechanism for continuous immune mediated control of active HIV replication even in the absence of detectable increases in peripheral blood of HIV specific T cells. However, the patients were maintained on antiretroviral therapy (ART) and thus the potential evaluation of antiviral control was not established.
In a nonhuman primate model, CD4+ T lymphocytes were collected prior to SIV infection to ensure a complete functional status of these cells. The result demonstrated that infusions of anti-CD3/28 expanded CD4+ T lymphocytes could induce antiviral responses with a capability to control SIV replication in vivo even after a cessation of ART [3 ]. Later on, an experiment was conducted in which CD4+ T lymphocytes were collected from SIV infected animals early postinfection. The result showed that a single round infusion of anti-CD3/28 expanded CD4 + T lymphocytes had the capacity to induce long-term control of viremia after ART cessation [4 ]. The results from both human and nonhuman primate demonstrated the safety and effectivity of autologous transfers of anti-CD3/28 expanded CD4 + T lymphocytes in improving their immune system to control viral replication.
In order to extend these findings to a clinical practice which need a large number of CD4+ T lymphocytes to be transferred to HIV-infected patients, cell expansion protocol to be used in the future clinical trial for HIV-infected patients need to be developed. Studies were conducted to optimize CD4+ T lymphocyte isolation and expansion protocol in both human and nonhuman primate [5,6 ]. Recently, our group demonstrated that the selection of cell isolation method might affect the expansion. Thus, purified CD4+ T lymphocytes which were isolated via immunorosette formation can be expanded up to 1000-fold within 3 weeks with high viability and high purity of CD4+ T lymphocytes [7 ].
However, defective CD4+ T lymphocytes in HIV-infected patients have already been documented. Numbers of evidences showed that phenotype and function of CD4+ T lymphocytes were different in each stage of HIV disease progression [ 8,9 ]. Therefore, CD4+ T lymphocyte expansion using anti-CD3/28 coated...