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TIM-3, a critical immune checkpoint in HIV research

Fri, 07/08/2016 - 11:47


CD4+ T-helper cells (Th) are the white blood lymphocytes expressing surface glycoprotein antigen CD4. These T-helper cells play an important role in the adaptive immune system by releasing T cell cytokines that help other immune cells to suppress or regulate immune responses. CD4+ T-helper lymphocytes can be divided into two types (Th1 and Th2) based on their cytokine secretion. Th1 cells are involved in cell-mediated immune response to intracellular pathogens and delayed-type hypersensitivity reactions. Th2 cells are involved in the immune response to extracellular infections and the promotion of allergic diseases.

T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), also known as HAVCR2, is a Th1-specific cell surface protein that serves as an immune checkpoint by inhibiting the immune response. Specifically, TIM-3 regulates macrophage activation, inhibits auto- and allo-immune responses, and promotes immunological tolerance. Researchers from various sub-areas of immunology are evaluating TIM-3 along with a number of other potential immune checkpoints including LAG3, BTLA, B7H3 and B7H4 for immunotherapy (Swatler et al., 2016). Due to its role in regulating immune response during HIV progression, TIM-3 antibodies have emerged as important tools in HIV research and immune system therapies in HIV patients.

TIM3 antibody

TIM3 Antibody

TIM3 antibody

Flow Cytometry analysis of TIM3 antibody (MAB2365) in human peripheral blood monocytes.

Flow Cytometry analysis of TIM3 antibody (NBP2-27220) in human peripheral blood monocytes.

Flow Cytometry analysis of TIM3 antibody (FAB2365P) in human peripheral blood monocytes.

Novus' monoclonal TIM-3 Antibody, clone 344823, is available in a variety of conjugated formats, including Phycoerythrin, Allophycocyanin, and AlexaFlour (R) dyes, and has been used in number of flow cytometry studies related to HIV immune response. For example, researchers used the unconjugated TIM-3 antibody (344823) (MAB2365) to demonstrate that soluble TIM-3 in human plasma may represent a new correlate of HIV disease progression (Clayton et al., 2015). In another recent study, Phycoerythrin conjugated format of this clone (FAB2365P) was used to show that a simple measurement of the CD4/CD8 ratio is a useful biomarker for assessment of combined CD4+ T cell dysfunction in chronic HIV disease (Frederiksen et al., 2015). Additionally, the per-CP conjugated format (FAB2365C) was used to monitor T cell phenotype and proliferation of HIV and HCV-specific T cells during interferon alpha therapy (Kared et al., 2014). Researchers also used Novus' goat polyclonal TIM-3 biotin conjugated antibody (BAF2365) to explore paths for therapeutic augmentation of HIV-specific CD4 (+) T cell function (Kassu et al., 2010). Together, these studies demonstrate how Novus' TIM-3 Antibodies have been used in flow cytometry analysis of various samples in HIV research.

Novus Biologicals offers a wide variety of quality guaranteed antibodies to TIM-3 and other immune checkpoint proteins for use in immunology, cancer and HIV research.

References:

  1. Swatler J, Kozłowska E. Immune checkpoint‑targeted cancer immunotherapies. Postepy Hig Med Dosw. 2016 Jan 26;70:25-42 [PMID: 26864062].
  2. Clayton KL, Douglas-Vail MB, Nur-ur Rahman AK, Medcalf KE, Xie IY, Chew GM, Tandon R, Lanteri MC, Norris PJ, Deeks SG, Ndhlovu LC, Ostrowski MA. Soluble T cell immunoglobulin mucin domain 3 is shed from CD8+ T cells by the sheddase ADAM10, is increased in plasma during untreated HIV infection, and correlates with HIV disease progression. J Virol. 2015 Apr;89(7):3723-36. [PMID: 25609823]
  3. Frederiksen J, Buggert M, Noyan K, Nowak P, Sönnerborg A, Lund O, Karlsson AC. Multidimensional Clusters of CD4+ T Cell Dysfunction Are Primarily Associated with the CD4/CD8 Ratio in Chronic HIV Infection. PLoS One. 2015 Sep 24;10(9) [PMID: 26402620]
  4. Kared H, Saeed S, Klein MB, Shoukry NH. CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals. PLoS One. 2014 Jul 9;9(7):e101441. [PMID: 25007250]
  5. Kassu A, Marcus RA, D'Souza MB, Kelly-McKnight EA, Golden-Mason L, Akkina R, Fontenot AP, Wilson CC, Palmer BE. J Immunol. 2010 Sep 1;185(5):3007-18. Regulation of virus-specific CD4+ T cell function by multiple co-stimulatory receptors during chronic HIV infection. [PMID: 20656923]

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